Keywords: Wolbachia
Editorial Overview – Insect Genomics (2026): enhancing public health, food security, and biodiversity through genetic biocontrol.
35506Yoosook Lee, Omar S. Akbari, Current Opinion in Insect Science, 2026-03-13 09:43:24.
Genetic biocontrol is a form of biological control in which genetic variants or genetically modified forms of the target species act to reduce or eliminate the target species. In entomology, target species include agricultural pests and vector species that transmit pathogens to human, animal, or plant systems. Examples include the Anopheles mosquito gene drive system to reduce or replace malaria vectors in Africa, the use of Wolbachia symbiont induced cytoplasmic incompatibility in Culex mosquitoes to project Hawaiian native birds from avian malaria related deaths, and the use of CRISPR to generate sterile males at a scale useful for suppressing pests of fruit crops. The widespread availability of robust transgenic technologies combined with new RNA-guided DNA endonuclease-based genome manipulation technologies and platforms and advances in synthetic biology are fueling the development of genetic biocontrol technologies and systems for combating arthropods that contribute to food insecurity, pathogen- and parasite-transmission, and invasive arthropods that threaten biodiversity. Heretofore a niche area of genetic biocontrol now commands great interest and an ever-growing number of applications.
Modelling Aedes albopictus management, incorporating immigration and bi-directional Wolbachia interactions
35520Ryan, M., Mendiolar, M., Pagendam, D. et al., J Pest Sci, 99. 2026-03-10 09:16:51.
Aedes albopictus mosquitoes are competent vectors for the spread of at least 24 different arboviruses, including dengue, Ross River, and Japanese encephalitis viruses. However, they remain less studied than their more urban cousins, Aedes aegypti. We model an incompatible insect technique (IIT) strategy for mosquito control, with bi-directional incompatibility between two strains of Wolbachia (wAlbA/wAlbB ARwP) and age-based cytoplasmic incompatibility decay in a well-mixed population. We include mosquito immigration to explore potential reversibility, an important consideration in bi-directional IIT control programs. We also explore the establishment probability after female contamination of an artificially-infected Wolbachia mosquito strain, consider the suppression dynamics and probability of mosquito management success for different release strategies, and determine a corresponding cost proxy for release (numbers of mosquitoes released). We found an establishment probability threshold of 40% in the absence of mating preferences, though this threshold needs validation in future field and laboratory experiments. We found differences in suppression success between release cessation and 6 months later for different immigration rates. There are similar short-term costs with differences in medium- and longer-term costs between release strategies. Our model suggests bi-directional IIT control programs are reversible with low amounts of wild-type immigration. This work demonstrates opportunities to optimise the suppression of these medically important mosquitoes.
Optimal spatial release strategies for confined gene drives and Wolbachia
35488Ziye Wang, Jackson Champer, bioRxiv, 2026-03-06 10:19:13.
Gene drives are genetic elements that can rapidly spread through populations, offering potential solutions for controlling disease vectors and pests. In some scenarios, it is necessary to utilize drives that can be confined to only target populations. The success of these threshold-dependent gene drives, which require a minimum local frequency to establish, depends critically on the spatial strategy used for introduction. Here, we use a reaction-diffusion model to systematically identify optimal release patterns that maximize the per-capita efficiency for four distinct gene drive designs as well as use of Wolbachia bacteria, which spread similarly to frequency-dependent gene drives. We find that the most efficient release strategy is highly dynamic, transitioning from a broad "everywhere" release for short timeframes to a "multiple-ring" pattern for intermediate times, and finally to a focused "center" release for longer timeframes. These timeframes depend on the specific type of drive, with more powerful variants transitioning more quickly to center releases. Our results demonstrate that these optimized, variable release strategies can be substantially more effective than simple uniform releases. This study provides a quantitative framework for designing effective gene drive implementations, highlighting that a carefully planned spatial strategy is essential for maximizing impact, making optimal use of available resources.
Wolbachia wMel and wAlbB strains differentially impact the vector competence of Aedes aegypti with a Brazilian genetic background for DENV-1 virus
35484Martins, C.B., David, M.R., Couto-Lima, D. et al., Parasites Vectors, 2026-03-05 08:32:23.
Aedes aegypti mosquitoes infected with the endosymbiotic bacterium Wolbachia pipientis have been released as a sustainable strategy to mitigate arbovirus transmission. Among the strains successfully deployed, wMel and wAlbB have shown promising blocking effects against dengue virus (DENV). However, the strength of viral inhibition depends on Wolbachia density within mosquito tissues, the genetic backgrounds of both host and virus, and the viral dose. In this study, we aimed to investigate the vector competence for DENV-1 of Ae. aegypti with Brazilian genetic background infected with wMel or wAlbB. A total of 493 wild and wMel- and wAlbB-infected mosquitoes were orally challenged with low (5 × 104 FFU/mL) and high (5 × 105) titers of DENV-1. Relative Wolbachia density was measured by quantitative polymerase chain reaction (qPCR), and viral infection in mosquito bodies and saliva was assessed by qPCR with reverse transcription (RT-qPCR). Transmission potential was tested through saliva microinjection into susceptible mosquitoes. The infection prevalence and viral loads in mosquito bodies were analyzed at 7, 14, and 21 days post infection (dpi).Both Ae. aegypti groups infected with wMel and wAlbB had reduced (albeit distinct) DENV-1 infection and transmission relative to wild type mosquitoes. wMel-infected mosquitoes exhibited less abundant bacteria in their bodies but a greater degree of DENV-1 inhibition compared with those carrying wAlbB, indicating that DENV-1 blocking is strain specific rather than Wolbachia density-driven. Moreover, we observed that Wolbachia had a protective effect on mosquitoes by decreasing the DENV-1 loads in their bodies, but with a constant presence of virus. Viral transmission rates in the saliva were similar among wild and wMel- and wAlbB-infected mosquitoes at 7 and 14 dpi but lower in wMel and wAlbB mosquitoes at 21 dpi. The similar DENV-1 loads in mosquito bodies over time (7, 14, and 21 dpi) infected with either the wMel or wAlbB strain, regardless of the viral titer of the infectious blood meal, suggest that Wolbachia may have a maximum pathogen-blocking capacity beyond which additional virus suppression cannot be achieved. The viral suppression only after 21 dpi in the saliva raises concerns and warrants further investigation, as females may transmit before Wolbachia blockage becomes effective. While wAlbB may exhibit comparable DENV-1 blocking to wMel, its enhanced thermal tolerance makes it epidemiologically relevant in tropical regions. Continuous monitoring of Wolbachia dynamics and DENV genomic variation in the field remains essential to evaluate long-term effectiveness and detect potential adaptive viral responses.
Locally Acquired Dengue in Townsville, Australia, 2024–2025: An Outbreak Report in a Non-Endemic Region with wMel Wolbachia-Infected Aedes aegypti
35533Thompson, K., Lyons, S., Malone, K., Fryk, J., Pyke, A., & Murton, K., Tropical Medicine and Infectious Disease, 11. 2026-02-26 19:11:49.
During the 2024/2025 wet season, Townsville had its first sustained autochthonous outbreak of dengue disease caused by dengue virus type 2 (DENV-2), the second locally transmitted outbreak of dengue since 2014 following the introduction of wMel strain Wolbachia-infected mosquitoes, a control strategy for dengue virus (DENV) and other Aedes-transmitted arboviruses. In comparison to two recorded locally acquired cases of dengue in 2020, the 2024/2025 outbreak resulted in sixteen cases in two inner-city suburbs of Townsville during the wet season associated with higher-than-average rainfall. This second dengue outbreak since 2014 highlights that Townsville and other north Queensland communities where Wolbachia mosquito programs have been deployed remain vulnerable to DENV incursions and local disease outbreaks despite the apparent high coverage of Wolbachia-infected mosquitoes. Whilst these control strategies have likely contributed to a reduction in the number and frequency of autochthonous DENV outbreaks in north Queensland, ongoing maintenance and monitoring of Wolbachia-infected mosquito coverage is necessary, together with timely review and improvement in dengue awareness and prevention health promotion activities in the community.
Mathematical modelling of Wolbachia replacement in Aedes aegypti for dengue control: a scoping review
35445Katie Tiley, Laith Yakob, Kathleen O'Reilly, Oliver Brady, Proc Biol Sci, 293. 2026-02-12 17:52:03.
Wolbachia replacement in dengue virus vectors is a promising tool for controlling transmission, and models can explore its potential in novel and complex scenarios. We analyse how research questions in Wolbachia replacement modelling have developed over time and in response to empirical findings. A scoping review was conducted of Wolbachia replacement models. For each study, we extracted research questions, key findings and modelling methodology and thematically categorized research questions. From 726 search results, 115 studies met inclusion criteria. Four themes were identified: identifying key Wolbachia characteristics (n = 61, 53.0%), investigating effects of environmental heterogeneity (n = 21, 18.3%), estimating epidemiological impact (n = 25, 21.7%) and exploring Wolbachia replacement in combination with other arboviral control measures (n = 8, 7.0%). Models identify cytoplasmic incompatibility (CI) and maternal transmission (MT) as key for fixation success. However, less than 20% (n = 6) of studies parameterize CI and MT using empirical sources. Although models agree outbreaks may occur with fixation, few explore epidemiological outcomes of heterogeneous Wolbachia fixation or combined vector control. These findings highlight the need for empirical parameterization and incorporating environmental complexity for models to remain insightful for decision-making. Policymakers would benefit from future models exploring heterogeneous coverage and combined control strategies, given evidence of context-specific outcomes and diverse control tools.
Dengue Suppression by Male Wolbachia-Infected Mosquitoes
35443Jue Tao Lim, Ph.D., Chee-Seng Chong, Ph.D., Chia-Chen Chang, Ph.D., et al., New England Journal of Medicine, 2026-02-12 17:46:04.
Wild-type female Aedes aegypti mosquitoes that mate with male A. aegypti mosquitoes that have been infected with the wAlbB strain of Wolbachia pipientis bacteria produce nonviable offspring owing to cytoplasmic incompatibility. Repeated releases of wolbachia-infected males can potentially suppress wild-type mosquito populations and reduce the risk of dengue virus infection. We conducted a trial involving the release of male A. aegypti mosquitoes infected with the wAlbB strain of wolbachia bacteria for the control of dengue in Singapore, a tropical city-state. In this cluster-randomized trial with test-negative controls, we divided 15 geographic population clusters into two groups: 8 clusters received deployments of male wolbachia-infected mosquitoes (intervention clusters) and 7 clusters received no deployments (control clusters). The primary end point was the diagnosis of symptomatic dengue virus infection of any severity caused by any serotype of the virus, as measured by the odds ratio for the distribution of wolbachia exposure among laboratory-confirmed reported dengue cases as compared with test-negative controls. A total of 393,236 residents lived in the intervention clusters, and 331,192 lived in the control clusters. Adult wild-type A. aegypti populations were suppressed across the intervention clusters. The baseline average abundance of the mosquitoes (number of adult female mosquitoes trapped divided by number of traps) was 0.18 and 0.19 in the intervention and control clusters, respectively; from 3 months after the initiation of the intervention until the end of the 24-month trial period, the average abundance was 0.041 and 0.277, respectively. In the intention-to-treat analysis at 6 months or more, the percentage of residents in the intervention clusters who were dengue-positive was lower than that in the control clusters (354 of 5722 tests [6%] vs. 1519 of 7080 tests [21%]). The protective efficacy of the intervention, calculated as (1−odds ratio)×100, ranged from 71 to 72% with 3 to 12 months or more of wolbachia mosquito exposure, as represented by odds ratios of 0.28 to 0.29. Release of sterile wolbachia-infected male A. aegypti mosquitoes reduced vector populations and the risk of dengue infection in Singapore.
Spatial Dynamics and Sterilization Range of Incompatible Aedes albopictus Males: Advancing Toward an Optimized IIT Approach
35474Lampazzi, E., Virgillito, C., Caputo, B., et al., Tropical Medicine and Infectious Disease, 11. 2026-02-06 18:17:05.
The Incompatible Insect Technique (IIT) is a species-specific, eco-friendly mosquito control method that relies on releasing Wolbachia-infected males, which induce cytoplasmic incompatibility (CI), rendering eggs inviable when mating with wild females. Aiming at optimizing IIT protocols in terms of cost-effectiveness, data on incompatible male dispersal and survival and the distance- and time-related impact of induced sterility are fundamental. This study plans to fill this gap and reports findings from a two-year field trial (2022–2023) at the ENEA-Casaccia Research Center, based on single-spot releases of incompatible Aedes albopictus males (ARwP strain). Male releases were carried out in late September 2022 (~15,000 released males) and the early Ae. albopictus season (at the end of June 2023; ~24,000 released males). Fifty-eight ovitraps were located at a 20–900 m distance from the ARwP release spot and were monitored weekly from May to November to assess egg hatching rates and measure CI effects in relation to both distance and time. Following the 2023 release, samples of adults were collected at increasing distances from the release site and at multiple post-release time points to assess, individually, wild female fertility and ARwP male dispersal and survival using Wolbachia as a genetic marker. Statistical analyses revealed that: (a) the highest reduction in the egg hatching was found within 100 m from the release spot (46.5% and 19.9%, respectively, in 2022 and 2023) but remained significant even at greater distances (29.9% and 7.7% at 300 m, respectively, in 2022 and 2023); (b) accordingly, the highest reduction in the wild female fertility occurred within 100 m from the release spot (47.3%), but similar effects were recognizable up to 600 m; (c) the overflooding ratio of the ARwP males did not significantly differ between 3 and 11 days after the release, with ARwP males remaining active up to 18 days and dispersing as far as 400 m. These results demonstrate the potential of localized, non-inundative IIT trials to furnish clues for the setup of spatially optimized release strategies, especially in scaled-up applications. The study also emphasizes the need for standardized assessment tools and further research regarding environmental and behavioral factors influencing long-term suppression outcomes.
Wolbachia mosquito release cuts dengue cases 50–80 percent
35437Mohamad Al As, Zaf Seraj, New Straits Times, 2026-01-27 18:26:15.
The release of Wolbachia-infected Aedes mosquitoes has led to a 50 to 80 per cent drop in dengue cases in several outbreak areas in Selangor, the Dewan Rakyat was told. Health Minister Datuk Seri Dr Dzulkefly Ahmad said public health studies conducted during the early phase of the programme showed encouraging results. "During the early phase of implementation, the results of public health studies in six dengue outbreak localities in Selangor showed a reduction in dengue cases between 50 per cent and 80 per cent compared with control localities," he said in a written parliamentary reply last night. He was responding to Mohd Hasnizan Harun (PN-Hulu Selangor), who asked whether the ministry has conducted comprehensive environmental and public health impact studies related to the release of Wolbachia-infected mosquitoes. Hasnizan also asked about continuous monitoring mechanisms to ensure long-term safety. Dzulkefly said the early assessments also examined the interaction between Wolbachia-infected Aedes mosquitoes and the existing mosquito population in the environment.
The Genomic Arms Race in Mosquito-Borne Diseases: Integrating Entomopathogenic Fungi, Gene Drive, and Symbiont Technologies for Sustainable Vector Control
35503Rajendran Yamini, Pagalahalli Sankaran Shanmugam, Marimuthu Murugan, et al., J Pure Appl Microbiol., 20:53-65. 2026-01-20 09:32:56.
Mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and lymphatic filariasis continue to impose enormous health and economic burdens worldwide. The traditional reliance on chemical insecticides has been undermined by the rapid evolution of resistance, ecological concerns, and declining efficacy. Next-generation biocontrol strategies are framed within the concept of a “genomic arms race” between mosquitoes, pathogens, and microbial agents. Entomopathogenic fungi are eco-friendly bioinsecticides with demonstrated efficacy in laboratory, semi-field, and transgenic applications. Symbiont-based approaches, particularly those involving Wolbachia, have been evaluated for their ability to reduce vector competence and spread through populations. Parallel advances in CRISPR-based gene drive technologies have provided transformative tools for population suppression and modification, although their deployment is limited by ethical, ecological, and regulatory concerns. An integrated vector management (IVM) framework combining fungi, gene drives, and symbiont-based tools is proposed as the most promising approach for sustainable mosquito management. This multipronged strategy has the potential to reduce disease transmission, delay resistance development, and minimize ecological disruption, paving the way for resilient, eco-friendly solutions against vector-borne diseases.
The symbiotic Wolbachia in Anopheles and its role in reducing the transmission of Plasmodium: updates and prospects
35359Nehra, R., Dhanda, S., Singh, K. et al., Archives of Microbiology, 208. 2026-01-14 11:49:05.
Reducing malaria transmission and the prospects for vector control include multi-pronged strategies, such as interrupting the parasite cycle in both vectors and mosquitoes. Effective vector control remains essential to prevent malaria transmission. This is all the more important as problems such as resistance to insecticides and the lack of a highly effective malaria vaccine remain. New generation vector control measures and optimised products are essential to address the public health needs for malaria eradication. Strategies to reduce malaria transmission include the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS) and other measures. Recent studies have shown that Wolbachia pipientis, a bacterium that acts as an intracellular endosymbiotic in host cells, is becoming increasingly popular as a new method of control for Anopheles mosquitoes, both for cytoplasmic incompatibility and for pathogen blocking. Anopheles gambiae, the infection rate ranged from 8 to 24% in the wild population of the same study in the case of An. coulzzi (WAnga) in Ghana, with a prevalence of 4%. Various studies have successfully identified Wolbachia in several species of Anopheles. A highly infected Anopheles species A population in the Democratic Republic of the Congo (DRC) showed a 91% infection rate (strain wAnsA). Broader surveys list additional species hosting natural Wolbachia, including An. funestus, An. moucheti, An. melas, An. nili, An. coustani, An. dirus, An. baimaii, An. hyrcanus, and An. sinensis, among others, totalling around 31 Anopheles species. In Anopheles stephensi, researchers achieved stable maternal transmission of the wPip strain with a 100% infection frequency in the transinfected line across generations. The infection caused nearly complete cytoplasmic incompatibility (CI) and moderate fitness costs. Previous experimental infections using the wAlbB strain in An. stephensi similarly established CI and partial protection against Plasmodium infection. Wolbachia has been detected naturally at low prevalence (~ 1.4%) in field-collected An. culicifacies samples in India. However, these infections are often rare and may not lead to a high blocking effect of the pathogens. Despite the notable progress in demonstrating the CI and moderate inhibitory effect of the pathogen in several Anopheles trans-infected lines, the remaining setbacks include persistent, mother-transmitted infection with a high population replacement or suppression potential that will be relevant for widespread use. This comprehensive evaluation identified the need for further research on host-symbiotic interactions, improved genetic engineering tools and comprehensive long-term field evaluations to fully realise the potential of Wolbachia as a vector control tool for malaria.
Wolbachia for malaria control
35347Zhang, Xinmi et al., Trends in Parasitology, 2026-01-08 10:34:56.
Malaria remains a major public health concern, and traditional vector control methods face growing challenges, underscoring the need for novel strategies. The success of Wolbachia-based dengue control, together with the establishment of Plasmodium-blocking Wolbachia transinfections in Anopheles, highlights the potential of a new tool for malaria control. This review discusses the main experimental systems for studying Wolbachia–Anopheles interactions, emphasizing the challenges of generating Wolbachia transinfected Anopheles gambiae strains. Experiments utilizing Plasmodium parasite challenge in transiently and stably infected Anopheles demonstrated that Wolbachia-induced Plasmodium suppression is feasible. Building on insights from Wolbachia–Aedes–arborvirus systems – and with current evidence from Anopheles systems – we also address mechanisms of Plasmodium suppression. Finally, we outline challenges and opportunities for translating these findings from proof-of-concept to field application.
Wolbachia as a transformative tool for mosquito-borne disease control: a comprehensive review of mechanisms, efficacy, and future directions
35325Minaei, M. E., Yousefi Nojookambari, N., Ghodraty, M., & Yazdansetad, S., Pathogens and Global Health, 2025-12-23 12:15:44.
Mosquito-borne infectious diseases such as dengue, Zika, chikungunya, and malaria continue to pose significant public health challenges worldwide. Traditional control methods, including the use of insecticides and environmental management, have shown limited effectiveness due to insecticide resistance and logistical challenges. Wolbachia-based strategies, which leverage the bacterium’s unique ability to manipulate mosquito reproduction and block pathogens, present a promising, albeit not universally applicable, method for reducing the transmission of mosquito-borne diseases. Field trials have demonstrated significant but variable efficacy. This systematic review synthesizes the latest findings on Wolbachia-based interventions, focusing on their mechanisms, efficacy, and potential for large-scale implementation. We conducted a comprehensive literature search across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published between 1990 and 2025. Our review highlights the promising results of Wolbachia-based strategies in reducing mosquito populations and disease transmission, while also addressing the challenges and limitations of this approach. We conclude that Wolbachia-based strategies hold great potential for revolutionizing mosquito-borne disease control, but further research and careful consideration of ecological and ethical implications are necessary for their successful implementation.
Analysis of a household-scale model for the invasion of Wolbachia into a resident mosquito population
35327Barlow, A., Penington, S. & Adams, B., Journal of Mathematical Biology, 92. 2025-12-22 12:18:25.
In areas infested with Aedes aegypti mosquitoes it may be possible to control dengue, and some other vector-borne diseases, by introducing Wolbachia-infected mosquitoes into the wildtype population. Thus far, empirical and theoretical studies of Wolbachia release have tended to focus on the dynamics at the community scale. However, Ae. aegypti mosquitoes typically dwell in and around the same houses as the people they bite and it can be insightful to explore what happens at the household scale where small population sizes lead to inherently stochastic dynamics. Here we use a continuous-time Markov framework to develop a stochastic household model for small populations of wildtype and Wolbachia-infected mosquitoes. We investigate the transient and long term dynamics of the system, in particular examining the impact of stochasticity on the Wolbachia invasion threshold and bistability between the wildtype-only and Wolbachia-only steady states previously observed in deterministic models. We focus on the influence of key parameters which determine the fitness cost of Wolbachia infection and the probability of Wolbachia vertical transmission. Using Markov and matrix population theory, we derive salient characteristics of the system including the probability of successful Wolbachia invasion, the expected time until invasion and the probability that a Wolbachia-infected population reverts to a wildtype population. These attributes can inform strategies for the release of Wolbachia-infected mosquitoes. In addition, we find that releasing the minimum number of Wolbachia-infected mosquitoes required to displace a resident wildtype population according to the deterministic model, only results in that outcome about 20% of the time in the stochastic model; a significantly larger release is required to reach a steady state composed entirely of Wolbachia-infected mosquitoes 90% of the time.
Rethinking the future of mosquito control
35341Kabirul Bashar, Dr Zonaed Siddiki. Dr Zonaed Siddiki, et al., Dhaka Tribune, 2025-12-17 11:37:26.
Bangladesh is once again in the grip of a severe dengue and chikungunya crisis in 2025. Hospitals are overwhelmed, fever wards are full, and doctors are working tirelessly. Families live in fear of mosquito bites, while daily news reports chronicle rising infections and deaths. As of December 16, 2025, the Directorate General of Health Services (DGHS) has reported more than 100,000 confirmed dengue cases and 409 deaths. However, this figure represents only the tip of the iceberg, as it reflects data solely from hospitalized patients, specifically from 77 hospitals in Dhaka and reports from 64 civil surgeon offices. A substantial number of dengue patients are receiving treatment at home or in various small and large hospitals and clinics that are not included in the official count. This underscores the overwhelming pressure on the country’s health system. At the same time, the Institute of Epidemiology, Disease Control and Research (IEDCR) has recorded a resurgence of chikungunya, reporting 337 suspected cases, 153 of which were laboratory-confirmed in Dhaka between January and May 2025. Researchers estimate that the true number of chikungunya infections this year may be close to one hundred thousand. As chikungunya testing is available only in a limited number of major hospitals in Dhaka, many cases remain undiagnosed and unreported.
Improving Wolbachia-based control programs in urban settings: Insights from spatial modeling
35335Florez D, Cortez R, Hyman JM, Qu Z, PLoS Neglected Tropical Diseases, 19. 2025-12-12 11:08:20.
Arboviral diseases remain a major public health concern, particularly in tropical and subtropical regions where mosquito populations thrive. One promising strategy to curb transmission is the release of Aedes aegypti mosquitoes infected with Wolbachia, a bacterium that reduces their ability to spread viruses. However, past large-scale releases have not always been successful, especially in complex urban settings, where restricted access to certain areas often leads to infection establishment failures and wasted resources. To address this, we developed a spatial model that simulates how Wolbachia-infected mosquitoes are established in different urban environments. We also explored strategies to improve their success under constraints on release size and the efficacy level of insecticide used for pre-release interventions. Our findings suggest that targeted releases are most effective in areas with limited mosquito movement without additional insecticide use. In higher-dispersal areas, reducing at least 35% of wild mosquitoes before release significantly improves establishment within nine months. Additionally, distributing releases over 2-5 weekly batches enhances success more than a single large release, even without other interventions. These findings offer practical insights for designing cost-effective and efficient Wolbachia-based mosquito control programs, reducing the burden of mosquito-borne diseases on vulnerable communities.
This scientist is breeding billions of mosquitoes to fight disease in Brazil
35301Mariana Lenharo, Nature, 2025-12-08 17:09:18.
nside a massive factory in the industrial district of Curitiba, Brazil, millions of Aedes aegypti mosquitoes are breeding in a climate-controlled room filled with mesh cages. Every week, the facility produces more than 80 million mosquito eggs. At the heart of this effort is Luciano Moreira, a soft-spoken agricultural engineer and entomologist, who opened the factory in July as part of an effort to fight mosquito-borne illnesses in the country. At the Curitiba facility, mosquitoes are infected with a bacterium called Wolbachia, which curbs the transmission of harmful human pathogens. Their offspring are being released in Brazilian cities to help to control dengue, a deadly viral disease transmitted mainly by A. aegypti. Until recently, Wolbachia-carrying mosquitoes were released only as part of small-scale research projects. The new factory marks a shift towards nationwide adoption of the method after Brazil’s federal government recognized it as an official public-health measure to combat dengue and other mosquito-borne diseases. People credit Moreira for making the case. “He has succeeded not only in carrying out the academic work, running experiments to demonstrate the model’s effectiveness, but also in convincing political decision-makers to implement the technology,” says Pedro Lagerblad de Oliveira, a molecular entomologist at Brazil’s Federal University of Rio de Janeiro. “This is a skill that not all scientists have.”
Wolbachia-Based biocontrol of Aedes aegypti: Current Progress, Challenges, and future prospects
35217Ashif Ahamed, Safdar Ali, Mehboob Hoque, Journal of Invertebrate Pathology, 2025-10-05 13:03:30.
Wolbachia is used as potential bio-control tool to reduce the dengue mosquitoes and also to reduce dengue virus (DENV) load in transinfected Aedes aegypti. Different field trials including the ones by the World Mosquito Program (WMP) have deployed Wolbachia carrying DENV primary vectors at different target sites worldwide. Field trials suggest that through the Population Replacement Strategy (PRS) and Incompatible Insect Technique (IIT), Wolbachia can introgress into the local Ae. aegypti population or reduce the population size of the Aedes aegypti by cytoplasmic incompatibility phenomenon and subsequent reduction in dengue incidences at target sites. Challenges for this strategy are to establish and maintain the transinfected mosquito population, choosing the appropriate strain of the bacteria, long term establishment of transinfected dengue mosquitoes for several subsequent generations, selecting the appropriate approach of mosquito field release, operational challenges, and the viral evolution. Moreover, the outcome of Wolbachia mediated biological control of Aedes aegypti in a broad scale is yet to be seen and the long-term stability of Wolbachia in transinfected mosquitoes remains unconfirmed. Significant success has been recorded in a broad scale deployment of wAlbB-carrying Aedes aegypti through the ongoing Wolbachia Malaysia project, resulting in a reduction in dengue fever cases. Successful large-deployment of this strategy has also been performed in Colombia and Indonesia (1.7 to 3.3 million people and 135–540 km2 area). Similar investigations on broad scale for longer period across different environmental conditions using transinfected mosquito deployment and associated risk analysis are imperative before adopting this biological control approach as a potent dengue control strategy worldwide.
Impact of larval diet on fitness outcomes of Aedes aegypti mosquitoes infected with wAlbB and wMelM
35213Md Yatim, M.F., Ross, P.A., Gu, X. et al., Parasites Vectors, 18. 2025-10-02 15:06:04.
Releases of Wolbachia-infected Aedes aegypti are being used to effectively control diseases caused by arboviruses, such as dengue. A well-balanced larval diet is essential for producing Wolbachia-infected mosquitoes with optimal fitness for release. In this study, four diets with varying protein-to-carbohydrate ratios were tested with three Ae. aegypti lines (carrying the wAlbB, wMelM Wolbachia infections or uninfected) to identify optimal diets for larval rearing on the basis of diet allocations ranging from 0.4 to 3.2 mg/larva/day. The diets were selected on the basis of a review of existing literature and are characterized by progressively increasing protein and decreasing carbohydrate content: diet 1 (Pd) was based on plant-based protein (low protein and high carbohydrate), diet 2 (Kd) was based on animal-based protein (moderate protein and high carbohydrate), diet 3 (Fd) involved Hikari fish food (high protein and moderate carbohydrate), and diet 4 (IAEA) followed a widely used very-high-protein and low-carbohydrate diet developed by the International Atomic Energy Agency (IAEA). The optimal concentration for each diet was determined using a fitness index that incorporated pupation success, fecundity, hatch proportion and development time. The optimal dietary allocations for diets 1–4 were 1.6, 1.2, 1.2 and 0.8 mg/larva/day, respectively, regardless of Wolbachia status. There was a consistent significant positive relationship between female wing length and fecundity in wAlbB (r2 = 0.881), wMelM (r2 = 0.329), and uninfected (r2 = 0.886) mosquitoes. Diet 3 (Fd) at optimal food allocation reduced a fitness cost commonly associated with the wAlbB line compared with the uninfected line when provided at the optimal concentration. The wMelM line showed a persistently low fecundity regardless of diet and concentration. These findings highlight the importance of an appropriate larval diet and dietary allocations in optimizing mosquito fitness for Wolbachia-based vector control programs. Further research into dietary composition, gut microbial interactions and Wolbachia associations could refine larval nutrition strategies, enhancing the effectiveness of mass-rearing for release programs.
Effect of egg irradiation on development and sterility of wild-type and Wolbachia trans-infected Aedes aegypti mosquito vectors
35170Kittayapong P, Ninphanomchai S, Thayanukul P, Limohpasmanee W, PLoS One, 20. 2025-09-26 13:56:46.
Sterile Insect Technique (SIT), Incompatible Insect Technique (IIT) or a combination of the two has become alternative promising vector control approaches. In order to apply these approaches, the targeted mosquitoes need to be sterilized and released. So far, the irradiation of mosquitoes has been conducted at the pupae or adult stages. In this study, we investigated the possibility of applying X-ray irradiation at the egg stage and also assessed the effect on the development and sterility of both wild-type and Wolbachia trans-infected Aedes aegypti mosquito vectors. The eggs of both wild-type and Wolbachia trans-infected lines were irradiated using X-ray at the doses of 1, 3, 5 and 7 Gy. Development of immature stages was observed. For wild-type Ae. aegypti, X-ray irradiation at the doses from 3 Gy decreased the development of the first-instar larvae and increased the development of the third-instar larvae but there was no effect on pupae. For Wolbachia trans-infected ones, a irradiation dose as low as 1 Gy could increase the development of the forth-instar larvae while an irradiation dose of 7 Gy induced significantly high mortality to the pupae (p < 0.05). To assess sterility, males and females that emerged from irradiated eggs were mated with the non-irradiated ones. Our results showed that an irradiation dose of 7 Gy significantly caused more than 90% sterility in both wild-type males and females (p < 0.05). However, this irradiation dose could be reduced to 5 Gy to sterilize both males and females infected with Wolbachia. Our findings revealed, for the first time, that applying a low-dose X-ray irradiation at the egg stage could sterilize both wild-type and Wolbachia trans-infected Ae. aegypti when they become adults. Egg irradiation could make the implementation of SIT, IIT or combined SIT/IIT for vector control much more feasible as the sterile eggs are easier to distribute and operate when compared to other developmental stages of mosquitoes.
Heterogeneity in inhibition of genetically diverse dengue virus strains by Wolbachia
35165Afeez Sodeinde, Emilie Finch, Ke Li, et al., bioRxiv, 2025-09-26 13:29:40.
The release of Aedes aegypti mosquitoes transinfected with the virus-inhibiting Wolbachia bacterium has the potential to reduce the burden caused by dengue virus (DENV). However, the robustness of this control strategy across the wide genetic diversity of DENV remains unknown. Here, we systematically tested two commonly used Wolbachia strains (wAlbB and wMelM) for their ability to inhibit 60 genetically diverse DENV isolates spanning all four serotypes. We found stronger inhibition by wMelM (median relative dissemination: 0.04) than wAlbB (median relative dissemination: 0.19). Furthermore, while we found substantial heterogeneity in inhibition across DENV isolates, we found that more DENV-3 isolates were weakly inhibited (median relative dissemination: 0.47 for wAlbB and 0.39 for wMelM) compared to the other serotypes (median relative disseminations: 0.10-0.18 for wAlbB and 0-0.11 for wMelM). Using transmission dynamic models, we further showed that differential Wolbachia inhibition results in increased probability of reemergence, particularly in high transmission intensity settings, with strong selection for DENV strains that have higher relative dissemination in mosquitoes. Our work highlights the importance of considering DENV genetic diversity, including the long-term risk of selection, in Wolbachia-based control interventions.
How billions of hacked mosquitoes and a vaccine could beat the deadly dengue virus
35143Lucila Pinto, Nature, 645:578-580. 2025-09-17 14:21:03.
Last month, a parade of vehicles wound its way through three cities in Brazil, releasing clouds of mosquitoes into the air. The insects all carry a secret weapon — a bacterium called Wolbachia that lowers the odds that the mosquitoes can transmit the dreaded dengue virus to humans. These infected mosquitoes are the latest weapon in Brazil’s fight against dengue, which infects millions of people in the country each year and can be fatal. A biofactory that opened in the town of Curitiba in July can produce 100 million mosquito eggs per week — making it the largest such facility in the world. The company that runs it, Wolbito do Brasil, aims to protect about 14 million Brazilians per year through its Wolbachia-infected mosquitoes. That will come as welcome news for the Brazilian health officials battling the rapidly growing threat of dengue. In 2024, the country experienced its worst outbreak yet: with 6.6 million probable cases and more than 6,300 related deaths. This year’s outbreak, although less severe, is also one of the highest on record, with 1.6 million probable cases so far (see ‘Dangerous outbreaks’). And the problem is spreading. Argentina, Colombia and Peru also experienced record-breaking outbreaks in 2024 and have seen a sustained increase in cases in recent years. Across Latin America and the Caribbean, deaths from dengue last year totalled more than 8,400 and the global figure reached more than 12,000 — the highest ever recorded for this disease.
The Urgent Need for More Research on Wolbachia-Based Mosquito Interventions in Public Health
35133Osvaldo Marinotti, Acta Tropica, 2025-09-15 15:36:56.
The release of Wolbachia pipientis-infected Aedes aegypti mosquitoes has emerged as a novel strategy to reduce the transmission of arboviruses such as dengue, chikungunya, and Zika. Wolbachia-based approaches to dengue control include population replacement, which reduces vector competence by establishing Wolbachia in wild populations of Aedes aegypti, and population suppression, which lowers mosquito densities through cytoplasmic incompatibility. Field trials of the population replacement strategy, based on wMel Wolbachia-infected mosquitoes, have shown variable success and concerns persist about long-term efficacy, safety and ecological impact. Uncertainties arise from an incomplete understanding of the mechanisms underlying pathogen blocking, possible bacteria and vector strain-specific effects, and the influence of environmental, host, and viral factors on the success of such a strategy. Moreover, some Wolbachia strains may enhance mosquito susceptibility to certain pathogens. Additionally, large-scale deployment raises the possibility of biodiversity disruption and the emergence of viral resistance. Given these unresolved concerns, it is premature and potentially irresponsible to expand the program to new areas without first rigorously assessing its safety, efficacy and sustainability.
Wolbachia Infection in Iranian Malaria Vectors: Prevalence and Biocontrol Implications
35124Shahin Saeedi, Fateh Karimian, Seyed Hassan Moosa-Kazemi, et al., Tropical Medicine & International health, 2025-09-08 08:50:24.
Wolbachia-based vector control is an emerging tool in malaria prevention research. This study evaluates Wolbachia infection in Iranian mosquitoes, focusing on seven known malaria vectors. Mosquitoes were collected from nine provinces of Iran (2016–2019), and Wolbachia infection status was analysed via PCR targeting eight genes: wsp, gatB, ftsZ, dnaA, groEL, gltA, CoxA and fbpA. We examined 1094 specimens from seven malaria vectors (Anopheles stephensi Liston, 1901; Anopheles culicifacies s.l. James, 1901; Anopheles fluviatilis s.l. James, 1902; Anopheles maculipennis s.l. Meigen, 1818; Anopheles sacharovi Favr, 1903; Anopheles dthali Patton, 1905; Anopheles superpictus s.l. Grassi, 1899), four non-malaria vectors (Anopheles mongolensis Linton, Lee and Curtis, 2005; Anopheles hyrcanus Pallas, 1771; Anopheles claviger Meigen, 1804; Anopheles turkhudi Liston, 1901) and three Culex species (Culex pipiens Linnaeus, 1758; Culex perexiguus Theobald, 1903; Culex theileri Theobald, 1903). PCR revealed Wolbachia DNA exclusively in An. dthali and Culex species, with infection rates of 73.4% for An. dthali and 77.78%–96.77% for Culex, notably higher in males. Wolbachia was detected in all regions except one in the north. Phylogenetic analysis revealed Wolbachia strains in An. dthali and Culex belong to supergroup B, closely related to strains in An. moucheti and An. demeilloni. This suggests broader applications for biocontrol strategies. The high Wolbachia prevalence in An. dthali is promising for malaria prevention. Future research should confirm cytoplasmic incompatibility and explore wAdth's potential to block malaria transmission.
Nature goes inside the world’s largest ‘mosquito factory’ — here’s the buzz
35120Adam Levy & Mariana Lenharo, Nature, 2025-09-08 08:31:27.
Raising mosquitoes to tackle disease might sound like an odd concept, but that’s what a facility in Brazil is aiming to do. Millions of mosquitoes are produced there every week, but these insects carry harmless Wolbachia bacteria that curbs their ability to spread deadly human viruses. Nature reporter Mariana Lenharo visited the facility and told us all about her experience in this Podcast Extra.
This is the world’s largest ‘mosquito factory’: its goal is to stop dengue
35109Mariana Lenharo, Nature, 2025-09-03 09:20:02.
When biologist Antonio Brandão tells people that he works at a mosquito factory, they are often baffled. Why would you make more mosquitoes?, he recalls people asking. “We have enough of them.” But once he explains that the laboratory-raised insects can help to stop the spread of dengue — which strikes hundreds of thousands in Brazil each year with fever, headache and bone pain — they come around. Brandão is the production manager, not at just any mosquito factory, but at the world’s largest, located in the southern Brazilian city of Curitiba. Launched in July, the facility is expected to produce 100 million eggs a week from the mosquito Aedes aegypti. However, unlike wild A. aegypti, the main transmitter of dengue virus, those churned out by the factory carry a harmless Wolbachia bacterium that curbs the insects’ ability to spread viruses including dengue and Zika. The idea is to release the modified mosquitoes, which researchers call wolbitos, into cities in Brazil, where they will mate with their wild counterparts and the females will pass the bacterium on to their offspring, gradually converting the local population. The wolbito strategy, which is being spearheaded by the non-profit World Mosquito Program (WMP), has already shown success in Colombia, Indonesia and at home: in the Brazilian city of Niterói in the southeast, dengue cases dropped by 69% in areas where Wolbachia-carrying mosquitoes were released, compared with areas where they weren’t1. Brazil’s federal government has adopted the approach to fight dengue infections — which surged to a record 6.5 million confirmed cases in the country last year — alongside other preventive measures such as vaccines.
Long-Term Durability and Public Health Impact of City-Wide wMel Wolbachia Mosquito Releases in Niterói, Brazil, During a Dengue Epidemic Surge
35107Anders, Katherine L., Gabriel Sylvestre Ribeiro, Renato da Silva Lopes, Pilar Amadeu, Thiago Rodrigues da Costa, Thais Irene Souza Riback, Karlos Diogo de Melo Chalegre, Wesley Pimentel de Oliveira, Cátia Cabral da Silva, Marcos Vinicius Ferreira Mendes B, Tropical Medicine and Infectious Disease, 10. 2025-09-02 18:57:03.
In 2024, the Americas experienced the largest dengue outbreak on record and Brazil was among the worst affected countries, reporting 6.6 million cases and 6200 deaths. We report the long-term entomological and epidemiological effectiveness of city-wide deployment of wMel-strain Wolbachia-infected Aedes aegypti in Niterói, a city of half a million people in Rio de Janeiro state, where Wolbachia releases across three-quarters of the urban population in 2017–2019 were expanded to remaining populated areas in 2023. wMel was durably established at ≥95% prevalence in Ae. aegypti populations throughout Niterói four years post-release, and up to seven years in the earliest release sites. Notified dengue case incidence in Niterói was 89% lower following Wolbachia releases, compared to the 10-year pre-intervention period of 2007–2016. Dengue incidence in Niterói in 2024, during a period of record high incidence in Brazil and the region, was 374 per 100,000 population, substantially lower than overall in Rio de Janeiro state (1884 per 100,000) and nationwide in Brazil (3157 per 100,000). Our findings show that city-wide Wolbachia coverage in Niterói provided sustained population-level reduction in dengue incidence throughout the five years post-intervention, including during the 2024 epidemic surge, averting an estimated three-quarters of the dengue case burden that may otherwise have been expected in Niterói in 2024.
Genomic Insights into Wolbachia Strain wCin2USA1 Reveal Promising Cytoplasmic Incompatibility Potential and Next-Generation Dengue Biocontrol
35098Istiaque Zaeem, Nurnabi Azad Jewel, Mohimenul Haque Rolin, et al., bioRxiv, 2025-09-01 19:59:21.
Dengue fever is one of the fastest-growing mosquito-borne diseases in the world, causing illness and economic challenges in many countries. Current mosquito control methods, such as insecticides, are often costly, less effective over time, and harmful to the environment. An alternative approach uses naturally occurring bacteria called Wolbachia, which live inside insects. When certain Wolbachia strains are introduced into mosquitoes, they can reduce the insects’ ability to spread viruses like dengue. In our study, we compared the genetic makeup of several Wolbachia strains to identify new candidates that may work better for controlling dengue. We discovered that a strain called wCin2USA1 has strong potential because it shares important features with two strains already used successfully, while also having unique advantages. These include genes that help prevent mosquitoes from reproducing normally when carrying different Wolbachia strains, which can reduce mosquito populations. Our findings suggest that wCin2USA1 could be developed as a new, environmentally friendly tool to help reduce dengue transmission.
How biotech helps Florida Keys prevent mosquito-borne diseases
35029Janine Stanwood, Local 10, 2025-08-17 19:49:34.
Biologists with the Florida Keys Mosquito Control District (FKMCD) are releasing lab-modified mosquitoes twice a week in the Middle Keys. It’s part of a pilot program to reduce the population and help stop people from getting bitten. “They’re male Aedes aegypti,” said Dr. Larry Hribar, FKMCD Director of Research. “They’re infected with a mosquito parasite that’s in the genus Wolbachia.” There are dozens of species of blood suckers in South Florida, including the nuisance salt marsh mosquito found in mangroves and in the Everglades. But it’s the Aedes aegypti that carries diseases like Zika and dengue. “That’s the one that vector the diseases we worry about,” said FKMCD spokesperson Chad Huff. The males, shipped from a company called MosquitoMate, have been infected with the Wolbachia bacteria before mating with females after being released. “They’ll find a local female, they’ll mate, but the eggs she produces are not going to be viable,” Hribar said. According to the Centers for Disease Control, the lab-infected mosquitoes can’t make people or animals sick.
Implications of successive blood feeding on Wolbachia-mediated dengue virus inhibition in Aedes aegypti mosquitoes
34989Johnson, R.M., Breban, M.I., Nolan, B.L. et al., Nat Commun, 16. 2025-07-30 10:55:57.
Wolbachia is a promising strategy to inhibit dengue virus (DENV) transmission by Ae. aegypti mosquitoes. Laboratory studies assessing DENV inhibition by Wolbachia typically have not considered natural frequent mosquito blood feeding behavior. Here, we determine the impact of successive feeding on DENV-2 transmission by Ae. aegypti in the presence or absence of Wolbachia (wAlbB and wMelM strains). We show that successive feeding shortens the extrinsic incubation period (EIP) in wildtype (WT; without Wolbachia) and wAlbB mosquitoes through enhanced dissemination. Feeding empirical data into models showed that successive feeding increases the probability of WT and wAlbB mosquitoes surviving beyond the EIP. Importantly, the more epidemiologically relevant comparison of the odds of wAlbB mosquitoes surviving beyond the EIP relative to WT, reveals a larger impact of successive feeding on WT than wAlbB. This indicates a strong inhibitory effect of Wolbachia even in the context of natural frequent mosquito blood feeding behavior.
Assessing the impact of the Wolbachia-based control of malaria
34962Zhuolin Qu, Lauren M. Childs, Mathematical Biosciences, 2025-07-08 13:34:58.
Malaria remains a significant infectious disease globally, causing hundreds of thousands of deaths each year. Traditional control methods, such as disease surveillance and mosquito control, along with the development of malaria vaccines, have made strides in reducing the disease’s impact, but new control methods are urgently needed. Wolbachia is a natural bacterium that can infect mosquitoes and reduce their ability to transmit diseases. While initially used to control dengue fever, recent research explored its potential for malaria control. In this study, we develop and analyze a novel mathematical model to assess the potential use of Wolbachia-based strategies for malaria control. The model describes the complex Wolbachia transmission dynamics among mosquitoes and incorporates key features of malaria transmission in humans with dynamical immunity feedback. We derive the basic reproduction number of the malaria disease transmission, which depends on the prevalence of Wolbachia in mosquitoes. Our findings reveal bifurcations in both Wolbachia transmission among mosquitoes and malaria transmission in humans, suggesting the potential for malaria elimination through Wolbachia-based interventions. The sensitivity analysis identifies the important parameters for the basic reproduction number and for malaria reduction and elimination. We numerically explore the integration of Wolbachia and other malaria controls. When control focuses on reducing the malaria burden in humans, there is a substantial rebound in malaria prevalence following the intervention in humans, and our results suggest post-Wolbachia malaria control leads to the greatest reduction in total days of infection. When Wolbachia release is integrated with pre-release mosquito control, there is a comparably large reduction in total days of infection if pre-release mosquito control occurs only a few days before Wolbachia release.
Dynamical analysis of a nonlocal delays spatial malaria model with Wolbachia-infected male mosquitoes release
34960Liping Wang, Runqi Liu, Yangyang Shi, Electronic Research Archive, 33:3177-3200. 2025-07-08 13:27:46.
Malaria continues to pose a considerable threat to global health. This study investigates the use of releasing Wolbachia-infected male mosquitoes as a method to mitigate the spread of malaria. We have formulated a reaction-diffusion model with nonlocal delays that includes the Wolbachia release strategy. The basic reproduction number R0 is defined within our model framework, serving as a critical threshold parameter that dictates the dynamic behavior of the model. A thorough dynamic analysis of the model reveals that when R0<1, a globally attractive infection-free steady state is established. In contrast, if R0>1, the disease persists uniformly. Numerical simulations are conducted to validate the theoretical results and to further illustrate the effectiveness of the Wolbachia release strategy on transmission and control of malaria. These simulations underscore the potential of using Wolbachia-infected male mosquitoes to significantly reduce spread of malaria.
Changes in the frequency of facultative endosymbionts in insect populations: overview and applications
34922Hoffmann, Ary A.; Cooper, Brandon S., Entomologia Generalis, 45:351-368. 2025-06-23 14:41:27.
Many insect endosymbionts are facultative from the host perspective, and their population frequencies across time and space will depend on their transmission fidelity and effects on host fitness. These effects and transmission rates in turn depend on the environmental and host genetic contexts where the endosymbionts occur. Endosymbionts like Wolbachia and Cardinium affect host reproduction to produce transient or persistent presence/absence polymorphisms, while other endosymbionts like Regiella and Hamiltonella persist through providing host fitness benefits and transmitting horizontally. Evolutionary changes in hosts and endosymbionts affect these impacts and endosymbiont polymorphisms in host populations and host sexes. We review this diversity of endosymbiont-host interactions and their influence on the usefulness of endosymbionts for applied strategies. Current strategies focus on endosymbionts driving useful traits to fixation (particularly Wolbachia suppression of arbovirus transmission by mosquitoes) or endosymbionts suppressing populations due to infected males sterilising females. Transinfected endosymbionts sourced from one species and microinjected into another have proven effective in these Wolbachia-mosquito strategies. Novel strategies involving transinfected Rickettsiella, Regiella and Wolbachia may decrease the impacts of pest invertebrates by suppressing pest numbers, reducing the capacity of vector hosts to transmit plant viral diseases or bolstering the effectiveness of natural enemies. Because many endosymbionts are already present in the environment, their applied use raises fewer safety concerns when compared to genetic modification, as supported by more than 13 years of field experiences with Wolbachia in mosquitoes that have not raised major concerns.
Drones To Deliver Millions Of Mosquitoes to Prevent Bird Extinctions In Hawai‘i
34913GrrlScientist, Forbes, 2025-06-11 19:19:54.
In a brilliant demonstration of multidisciplinary collaboration, a conservation program to save Hawai’i’s critically endangered native bird species has taken another step forward. After a team of scientists created “reproductively incompatible” male mosquitoes in the lab, the next challenge was to safely deliver them to where they would most effectively suppress mosquito populations in Hawai’i. “Reproductively incompatible” male mosquitoes are created by infecting their mothers with the bacteria, Wolbachia. This bacteria, which naturally occurs in many wild insect species, interferes with reproduction in mosquitoes by making the Wolbachia-males reproductively incompatible with normal wild-type female mosquitoes. (But the males can successfully reproduce with females infected with the same strain of Wolbachia – that is how the millions of mosquitoes needed for this project are produced in the lab.) When these reproductively incompatible Wolbachia-male mosquitoes mate with normal wild female mosquitoes, the resulting eggs cannot hatch, thereby reducing the mosquito population. The good news in this story (which will become important as you read on) is that male mosquitoes (regardless of whether they carry Wolbachia) do not bite or transmit disease, and feed only on plant juices and nectar for survival and energy. On the other hand, female mosquitoes do bite because they need a fresh blood meal to produce eggs. Additionally, because mosquitoes infected with Wolbachia bacteria are not genetically modified, and because Wolbachia bacteria naturally occur in 60% or more wild insects, these mosquitoes are safe.
Unstable laboratory Wolbachia strain w-Anga is negatively correlated with Plasmodium falciparum in wild malaria vectors
34856Estelle, D.L., Jacques, G.E., Issiaka, S. et al., Scientific Reports, 15. 2025-05-26 20:48:59.
Spread of insecticides resistance threatens the control of malaria. In this context, biological control using an endosymbiotic bacterium Wolbachia is being explored as a complementary method for its control. However, for optimal use of this bacterium in biocontrol strategies, it is imperative to characterize it. So, Anopheles gambiae complex mosquitoes were collected, morphologically identified, then blood fed and gravid female mosquitoes oviposited individually. After oviposition, the species of parent was molecularly determined, along with their w-Anga infection status. Additionally, we performed 16SrRNA gene sequencing of w-Anga-positive mosquitoes to determine their phylogeny. Finally, we amplified gene encoding the circumsporozoite protein to determinate their Plasmodium falciparum infection status and assessed the stability of w-Anga transmission of positive females and their offspring. From the results obtained, our w-Anga strains cluster with other Wolbachia Supergroup B strains. However, the prevalence of Plasmodium falciparum infection was lower in Wolbachia-infected females (4.59%) than in those uninfected (22.02%). Furthermore, the transmission frequency of this bacterium in infected Anopheles coluzzii females of the F0 generation to F1 offspring was 10.64% and 16.67% from infected females of the F1 generation to F2 offspring. This study results will serve as preliminary data for the possible use of Wolbachia in malaria control.
Mosquito Miracle: Breakthrough Brings Hope for Bangladesh in Dengue Fight
34837Staff Correspondent, Digi Bangla Tech, 2025-05-10 19:42:52.
A major scientific breakthrough is offering new hope for Bangladesh in its battle against dengue. An international team of researchers has successfully developed a strain of Aedes aegypti mosquitoes infected with Wolbachia bacteria, which are capable of adapting to the local environment of Dhaka city. Dubbed as “good mosquitoes,” this innovation opens a new, safe, and biological pathway for controlling the spread of dengue and other mosquito-borne arboviral diseases in the country, according to the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The research team includes scientists from QIMR Berghofer Medical Research Institute in Australia, the University of Queensland, icddr,b, and the United States Centers for Disease Control and Prevention. The findings were recently published in the journal Nature’s Scientific Reports. According to icddr,b, dengue has emerged as a severe public health threat in Bangladesh. In 2023 alone, a record 321,000 people were infected, with more than 1,700 deaths—making it the deadliest year on record. Rapid urbanization, erratic rainfall, and rising temperatures have contributed to the spread of Aedes mosquitoes, the primary vector of dengue. Simultaneously, the effectiveness of conventional insecticide-based mosquito control methods is declining due to growing resistance among mosquito populations. This has prompted scientists worldwide to seek more sustainable solutions, with the use of "good mosquitoes" being one of the most promising. Researchers explained that Wolbachia was chosen because it prevents Aedes mosquitoes from transmitting dengue, chikungunya, and Zika viruses, without harming humans or the environment. Wolbachia is a naturally occurring bacterium found in butterflies, fruit flies, and some mosquito species, though not in Aedes aegypti. This bacterium cannot infect humans or animals, nor is it transmissible through bites or contact.
Economic evaluation of Wolbachia deployment in Colombia: A modeling study
34812Shepard, D.S., Lee, S.R., Halasa-Rappel, Y.A., Rincon Perez, C.W., Harker Roa, A., PLoS One, 20. 2025-05-04 15:55:06.
Wolbachia are bacteria that inhibit dengue virus replication within the mosquito. A cluster-randomized trial in Indonesia found Wolbachia reduced virologically-confirmed dengue cases by 77.1%. Previous models predicted Wolbachia to be highly cost-effective in Indonesia, Vietnam, and Brazil. To inform decisions about future extensions in Colombia, we performed economic evaluations of potential Wolbachia deployments in 11 target cities. We assembled the numbers and distribution by severity of reported dengue cases from Colombia’s national disease surveillance system and the health service provision registry (RIPS). An epidemiological panel of three experts estimated the shares of dengue that were non-medical, under-reported, or misreported as another disease. We determined costs (in 2020 US dollars at market prices) of treating dengue illness from the benchmark insurance tariff and RIPS data on treatment services per symptomatic dengue case. Our central estimates projected 10 years of efficacy and focused on Cali, the target city with the highest number of dengue cases. For Cali, we estimated a net health-sector savings of US$4.95 per person and averting 369 disability-adjusted life years (DALYs) per 100,000 population. From a societal perspective, at 10 years Wolbachia deployment is expected to have highly favorable benefit-cost ratios, with benefits per dollar invested of US$5.50 in Cali and US$4.68 over all target cities. Over 10 years, Wolbachia is highly beneficial on economic grounds, and almost universally cost saving. The Wolbachia program’s economic benefits exceeded its costs in all 11 cities. The program’s savings in healthcare costs alone would more than offset deployment costs nationally and in 9 of 11 target cities. Wolbachia is likely to be the most cost-effective or cost-saving dengue control option in municipalities with both high incidence of dengue and high population density, whereas areas with high dengue incidence but low population density should consider vaccination.
Wolbachia: A bacterial weapon against dengue fever- a narrative review of risk factors for dengue fever outbreaks
34743Safaei, S., Derakhshan-Sefidi, M., Karimi, A., New Microbes and New Infections, 65. 2025-04-04 14:53:55.
Arboviruses constitute the largest known group of viruses and are responsible for various infections that impose significant socioeconomic burdens worldwide, particularly due to their link with insect-borne diseases. The increasing incidence of dengue fever in non-endemic regions underscores the urgent need for innovative strategies to combat this public health threat. Wolbachia, a bacterium, presents a promising biological control method against mosquito vectors, offering a novel approach to managing dengue fever. We systematically investigated biomedical databases (PubMed, Web of Science, Google Scholar, Science Direct, and Embase) using “AND” as a Boolean operator with keywords such as “dengue fever,” “dengue virus,” “risk factors,” “Wolbachia,” and “outbreak.” We prioritized articles that offered significant insights into the risk factors contributing to the outbreak of dengue fever and provided an overview of Wolbachia's characteristics and functions in disease management, considering studies published until December 25, 2024. Field experiments have shown that introducing Wolbachia-infected mosquitoes can effectively reduce mosquito populations and lower dengue transmission rates, signifying its potential as a practical approach for controlling this disease.
Comparison of oviposition and adult trapping to monitor wMel introgression for Wolbachia-based vector control
34738Nelson, E., Pereira, T.N., Ribeiro E., et al., bioRxiv, 2025-04-03 17:36:42.
Wolbachia introgression into Aedes aegypti mosquito populations has been shown to be effective in preventing dengue and is being evaluated for WHO prequalification. Monitoring the long-term introgression of Wolbachia (wMel)-positive Aedes aegypti mosquitoes, however, requires labor-intensive and costly BG-Sentinel traps (BG-traps). More affordable alternatives, such as using oviposition traps (ovitraps), have not been fully evaluated. Ae. aegypti eggs and adults were collected from 124 ovitraps and 237 BG-traps, respectively, across 12 clusters in Belo Horizonte, Brazil from March to May 2023 as part of the EVITA Dengue trial. We used a qPCR assay to detect wMel in a sample of L3-L4 stage larvae (up to 29) that were reared from eggs in ovitraps and adults from BG-traps (up to 10 per BG-trap). We used mixed effects models to compare estimates of cluster-level wMel introgression from ovitrap and BG-trap data over time. Among 3,675 larvae reared from ovitraps, wMel prevalence was 0.50 (95% CI: 0.48-0.51). Among 1,244 adult Ae. aegypti tested from BG-traps, wMel prevalence was 0.45 (95% CI: 0.42-0.48). Cluster-level wMel introgression in larvae and adults was highly correlated (Spearman’s r = 0.70, p = 6.71e-06). Multivariate analysis found that ovitrap estimates of introgression were associated with BG-trap estimates in the same month when models incorporated the previous month’s ovitrap wMel-positive count, the proportion of wMel in ovitraps in the current and previous month, and Ae. aegypti abundance. Leveraging this model, predicted wMel introgression from ovitrap data were highly correlated with observed introgression from BG-trap data (rs,counts=0.98, p=1.53e-14; rs,prevalences=0.82, p=0.11e-05) and provided greater precision than crude ovitrap-based estimates.
Global asymptotic stability in a delay stage structured model for mosquito population suppression
34720Huang, Mg., Yu, Js., Applied Mathematics, 40:112-136. 2025-03-31 14:42:25.
A promising avenue to control mosquito-borne diseases such as dengue, malaria, and Zika involves releasing male mosquitoes carrying the bacterium Wolbachia in wild areas to drive female sterility by a mechanism called cytoplasmic incompatibility (CI). In this work, we initiate a preliminary assessment of how the combined impact of dispersal, incomplete CI and mating competitiveness on mosquito population suppression by a delay differential equation model. Our theoretical analyses indicate that the immigration of eggs plays a significant role in the suppression dynamics. For the case without egg immigration, we identify a threshold dispersal rate v* of adult mosquitoes, threshold CI density ξ*, and threshold release ratio r*. A successful mosquito suppression would be established only when v < v*, ξ > ξ*, and r(t) ≥ r* uniformly. The immigration of eggs causes the threshold dynamics to be invalid, and warns an absolute failure of population suppression. The monotonicity of the adult steady-state in the dispersal rate and CI intensity indicates that choosing a suitable Wolbachia strain with strong CI intensity, or bringing down the dispersal rate of mosquitoes by blocking the suppression zones is a feasible strategy to obtain a better suppression level.
Exploiting Wolbachia as a Tool for Mosquito-Borne Disease Control: Pursuing Efficacy, Safety, and Sustainability
34677Moretti, R., Lim, J. T., Ferreira, A. G. A., et al, Pathogens, 14:285. 2025-03-28 09:41:16.
Despite the application of control measures, mosquito-borne diseases continue to pose a serious threat to human health. In this context, exploiting Wolbachia, a common symbiotic bacterium in insects, may offer effective solutions to suppress vectors or reduce their competence in transmitting several arboviruses. Many Wolbachia strains can induce conditional egg sterility, known as cytoplasmic incompatibility (CI), when infected males mate with females that do not harbor the same Wolbachia infection. Infected males can be mass-reared and then released to compete with wild males, reducing the likelihood of wild females encountering a fertile mate. Furthermore, certain Wolbachia strains can reduce the competence of mosquitoes to transmit several RNA viruses. Through CI, Wolbachia-infected individuals can spread within the population, leading to an increased frequency of mosquitoes with a reduced ability to transmit pathogens. Using artificial methods, Wolbachia can be horizontally transferred between species, allowing the establishment of various laboratory lines of mosquito vector species that, without any additional treatment, can produce sterilizing males or females with reduced vector competence, which can be used subsequently to replace wild populations. This manuscript reviews the current knowledge in this field, describing the different approaches and evaluating their efficacy, safety, and sustainability. Successes, challenges, and future perspectives are discussed in the context of the current spread of several arboviral diseases, the rise of insecticide resistance in mosquito populations, and the impact of climate change. In this context, we explore the necessity of coordinating efforts among all stakeholders to maximize disease control. We discuss how the involvement of diverse expertise—ranging from new biotechnologies to mechanistic modeling of eco-epidemiological interactions between hosts, vectors, Wolbachia, and pathogens—becomes increasingly crucial. This coordination is especially important in light of the added complexity introduced by Wolbachia and the ongoing challenges posed by global change.
Adjacent spillover efficacy of Wolbachia for control of dengue: emulation of a cluster randomised target trial
34679Lim, J.T., Mailepessov, D., Chong, C.S. et al., BMC Medicine, 23. 2025-03-28 08:29:31.
Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wild-type females yield non-viable eggs, thereby suppressing Ae. aegypti abundance in the field. We evaluated the spillover efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue in sites adjacent to release sites (spillover sites). The protocol of a two-arm cluster-randomised test-negative controlled trial (cRCT) was specified and emulated using a nationally representative dengue test-negative/positive database of 454,437 individuals reporting for febrile illness to primary or secondary care in public healthcare institutions. Spillover intervention sites were defined by geolocating locations which were adjacent to, i.e. shared geographical borders with, actual Wolbachia intervention sites. We built a cohort of individuals who resided in spillover sites versus a comparator control group who resided in sites which did not receive Wolbachia interventions. We emulated a constrained randomisation protocol used in cRCTs to balance dengue risk between spillover and control arms in the pre-intervention period. We matched individuals reporting for testing in intervention and control groups by calendar time and a high-dimensional battery of sociodemographic, environmental and anthropogenic variables. Intention-to-treat analysis was conducted to estimate the protective efficacy against dengue given spillover Wolbachia exposure. The final cohort consisted of 2354 matched individuals residing in Wolbachia spillover and control sites for at least 3 months in the study period. Compared to the controls, individuals residing in spillover sites for 3 or more months were associated with a 45% (OR: 0.55, 95% CI: 0.42‒0.74) reduction in risk of contracting dengue. Higher durations of spillover Wolbachia exposure also modestly increased protective efficacies. Compared to the control arm, the proportion of virologically confirmed dengue cases was lower in the spillover arm overall and across each subgroup. Protective efficacies were found across all years, age and sex subgroups. Our results demonstrated the potential of Wolbachia-mediated sterility for reducing the risk of contracting dengue even in sites which were not directly treated by the intervention.
Mark-Release-Recapture of Packed and Shipped Aedes aegypti with Wolbachia: Implications for Conducting Remote Incompatible Insect Technique Programs
34640Ohm, J. R., Lynd, A., McGowan, A., et al., The American Journal of Tropical Medicine and Hygiene, 2025-03-21 14:44:30.
Male mosquitoes containing the endosymbiont Wolbachia (Wb+) can be used as a tool to suppress wild mosquito populations through a technique termed incompatible insect technique (IIT). IIT programs reduce wild mosquitoes via incompatible matings between released males and wild females to reduce the number of viable offspring produced in the next generation. Successful programs rely on regular release of incompatible males to outcompete wild males for female mates. Past IIT programs have relied on local production of Wb+ males to support regular releases of incompatible males. Here, we evaluated the survival and dispersal of packed and shipped Wb+ Aedes aegypti males in mark-release-recapture studies at a release site in the British Virgin Islands (BVI), separated by over 3,600 miles from the centralized production facility. Released mosquitoes were recaptured using BG-Sentinel 2 traps collected daily for up to 7 days after release. Wb+ male mosquitoes packed and shipped from a centralized production facility performed similarly to males that were locally reared in the BVI in survival, dispersal, and recapture rates. Our results support the conclusion that packing and shipping live Wb+ male mosquitoes does not impact their ability to survive and disperse in release sites and suggests that IIT mosquito control programs can feasibly be conducted nearly anywhere in the world without the need for local mosquito production facilities.
wStri spread dynamics in Nilaparvata lugens via discrete mathematical models
34574Zheng, B., Yang, H., Elaydi, S. et al., Journal of Mathematical Biology, 90. 2025-03-12 16:30:16.
Wolbachia, an intracellular bacterium, is well-known for inducing cytoplasmic incompatibility, which has become a promising and environmentally sustainable strategy for controlling pest populations. The strain wStri, specifically identified in Nilaparvata lugens (brown planthopper), has shown potential for such biocontrol applications. In this study, we develop a comprehensive discrete mathematical model to analyze the dynamics of wStri spread in a mixed population of wStri-infected, wLug-infected, and uninfected Nilaparvata lugens under both constant and periodically varying environmental conditions. Under a constant environment, the model identifies the critical threshold necessary for the successful establishment of wStri within the population. Our analysis reveals that the model exhibits a strong Allee effect, where a population must exceed a certain critical density-the Allee threshold-for the wStri strain to persist and spread. Below this threshold, the wStri strain is likely to be eliminated, failing in pest control efforts. When the environment varies periodically, the model transforms into a non-autonomous periodic discrete model, introducing additional complexity. In this scenario, we derive sufficient conditions that ensure the composition of finitely many Allee maps continues to function as an Allee map. Furthermore, we prove that a unique periodic orbit exists within such a periodic environment. This orbit is characterized as unstable and acts as a threshold, determining whether wStri will establish itself in the population or die out over time. The findings from this model provide critical insights into the conditions under which wStri can be effectively used to control Nilaparvata lugens, particularly in environments that are not constant but fluctuate periodically. These insights have significant implications for the practical deployment of Wolbachia-based biocontrol methods in pest management strategies.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34543Bhattacharyya, J., Roelke, D.L., Acta Tropica, 262. 2025-02-25 10:59:30.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Implications of successive blood feeding on Wolbachia-mediated dengue virus inhibition in Aedes aegypti mosquitoes
34529Rebecca M. Johnson, Mallery I. Breban, Braiya L. Nolan, et al., bioRxiv, 2025-02-21 10:22:32.
Dengue virus (DENV) is a mosquito-borne virus that poses a continued and increasing threat to public health. A promising strategy to mitigate the burden of DENV is introgression of the virus-inhibiting Wolbachia pipientis bacterium into Aedes aegypti populations in the field. While previous studies on Wolbachia-mediated virus inhibition have typically assessed viral replication following a single bloodmeal, the main vector of DENV, Ae. aegypti, feeds frequently, often biting multiple hosts per gonotrophic cycle and promptly attempting to refeed following egg laying. Previously, we demonstrated that successive blood feeding reduces the extrinsic incubation period (EIP) and shortens the time it takes for a mosquito to be able to transmit viruses to a new host. With this in mind, we investigated the impact of successive blood meals on DENV serotype 2 (DENV-2) in Ae. aegypti in the presence or absence of Wolbachia (wAlbB and wMelM). We found that both WT and Wolbachia transinfected had increased DENV-2 dissemination 7 days post-infection as well as higher body titers of DENV-2 in the double-fed groups. Using these empirical data in a binomial regression model, we estimated that successive feeding increased the probability of WT and Wolbachia transinfected mosquitoes surviving the EIP. When we estimated the odds of surviving the EIP for mosquitoes with Wolbachia relative to WT mosquitoes, successive feeding increased the chances of WT mosquitoes surviving the EIP more than in mosquitoes with Wolbachia, indicating a strong inhibitory effect of Wolbachia even in the context of natural frequent blood feeding behavior. Our work shows that mosquito feeding behavior should be considered when assessing the inhibitory effects of Wolbachia on DENV.
Suppression of Aedes aegypti may not affect sympatric Aedes albopictus populations: findings from two years of entomological surveillance in Singapore
34497Wong, W.J., Tan, C.H., Verkaik, M.G. et al., Scientific Reports, 15:2253. 2025-02-04 19:28:45.
Globally, multiple trials have successfully demonstrated the effectiveness of novel tools, such as the sterile and incompatible insect techniques, in suppressing Aedes aegypti populations. However, there is concern that Aedes albopictus, another arbovirus-competent vector, may occupy the niches vacated by Ae. aegypti in areas where these species occur in sympatry. Here we investigate these concerns within the context of a Wolbachia-based Ae. aegypti suppression programme in highly urban Singapore, where general mosquito management is sustained through environmental management. Using nationally representative and longitudinal Aedes surveillance data, we show (1) no consistent association of increase in Ae. albopictus abundance with Ae. aegypti population suppression within Wolbachia-Aedes release sites, and (2) no significant change in the vertical spatial distribution of Ae. albopictus in high-rise residential apartment blocks even after two years of Ae. aegypti suppression. Finally, we report that dengue viruses were less prevalent in field Ae. albopictus than in Ae. aegypti, which is consistent with previous findings that Ae. albopictus is a lesser vector than Ae. aegypti in Singapore. Together, these results indicate that suppression of Ae. aegypti in the community may not be directly associated with any increase of Ae. albopictus population or capacity. Nonetheless, the risk of increase in Ae. albopictus population is anticipated if the reduction in disease transmission leads to less aggressive source reduction efforts and environmental management for mosquito control.
Wolbachia-Based Approaches to Controlling Mosquito-Borne Viral Threats: Innovations, AI Integration, and Future Directions in the Context of Climate Change
34249Branda, F., Cella, E., Scarpa, F., et al., Viruses, 16:1868. 2025-01-13 14:55:50.
Wolbachia-based mosquito control strategies have gained significant attention as a sustainable approach to reduce the transmission of vector-borne diseases such as dengue, Zika, and chikungunya. These endosymbiotic bacteria can limit the ability of mosquitoes to transmit pathogens, offering a promising alternative to traditional chemical-based interventions. With the growing impact of climate change on mosquito population dynamics and disease transmission, Wolbachia interventions represent an adaptable and resilient strategy for mitigating the public health burden of vector-borne diseases. Changes in temperature, humidity, and rainfall patterns can alter mosquito breeding habitats and extend the geographical range of disease vectors, increasing the urgency for effective control measures. This review highlights innovations in Wolbachia-based mosquito control and explores future directions in the context of climate change. It emphasizes the integration of Wolbachia with other biological approaches and the need for multidisciplinary efforts to address climate-amplified disease risks. As ecosystems shift, Wolbachia interventions could be crucial in reducing mosquito-borne diseases, especially in vulnerable regions. AI integration in Wolbachia research presents opportunities to enhance mosquito control strategies by modeling ecological data, predicting mosquito dynamics, and optimizing intervention outcomes. Key areas include refining release strategies, real-time monitoring, and scaling interventions. Future opportunities lie in advancing AI-driven approaches for integrating Wolbachia with other vector control measures, promoting adaptive, data-driven responses to climate-amplified disease transmission.
Recommendations for Implementing Innovative Technologies to Control Aedes aegypti: Population Suppression Using a Combination of the Incompatible and Sterile Insect Techniques (IIT-SIT), Based on the Mexican Experience/Initiative
34247Martín-Park, A., Contreras-Perera, Y., et al., Insects, 15:987. 2025-01-13 11:41:22.
The future of Aedes aegypti control emphasizes the transition from traditional insecticides toward more sustainable and multisectoral integrated strategies, like using Wolbachia-carrying mosquitoes for population suppression or replacement. We reviewed the integration of the successful Mexican initiative, “Mosquitos Buenos”, with the key challenges outlined in the PAHO guidelines for incorporating innovative approaches into vector control programs. These challenges include establishing essential infrastructure, training personnel, managing field operations, and fostering community support. Our experience provides critical evidence to support the strategic National Plan for implementing and integrating IIT-SIT technologies to control Ae. aegypti and dengue. Furthermore, this experience serves as a foundation for other countries in the region interested in adopting these technologies. It underscores the importance of strategic planning, multisectoral collaboration, continuous evaluation, and scaling up innovative tools to ensure their long-term effectiveness and sustainability in urban areas where Aedes vectors and the diseases they transmit are endemic.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34213Joydeb Bhattacharyya, Daniel L. Roelke, Acta Tropica, 262. 2025-01-07 09:07:50.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Mitigating dengue transmission in Africa: the need for Wolbachia-infected mosquitoes’ rollout
34211Samson Ogunlade, Adeshina Adekunle, Emma McBryde, Frontiers, 12. 2025-01-07 08:57:15.
Dengue fever is a mosquito-borne viral disease that poses a significant public health concern globally. The disease is primarily transmitted by Aedes aegypti mosquitoes and the range of clinical manifestations vary from flu-like symptoms to more serious conditions such as dengue haemorrhagic fever and dengue shock syndrome. The dengue virus (DENV) infects about 400 million people yearly, of which 50–100 million of those become symptomatic, with over 20,000 deaths. Dengue notifications are increasing in Africa. The continent's tropical and subtropical climatic conditions create a conducive breeding environment for mosquitoes and hence, contribute to the spread of the virus. While recent statistics show that there were 15.7 million reported dengue infections in 2010, recent studies show that dengue cases are on the rise in Africa. This situation presents an increasing threat to public health systems already under pressure from other infectious illnesses. Traditionally established vector control methods such as the use of insecticide, emptying or covering water-filled containers and eliminating mosquito breeding sites have had limited success in curbing the spread of dengue. This calls for experimental and innovative strategies to combat the disease effectively. One promising approach—the Wolbachia-based approach, involves the deployment of Wolbachia-infected mosquitoes into the wild mosquito population. This technique has shown great potential in reducing dengue transmission. While the Wolbachia-based technique has demonstrated highly positive results in mitigating DENV, it is not always successful—Wolbachia strategies may struggle in high temperature settings, because some mosquitoes infected with Wolbachia (such as wMel strain) are unable to transmit Wolbachia maternally to their offspring and establish themselves under high temperatures. Therefore, using thermally tolerant strains may be beneficial in establishing Wolbachia infections in mosquitoes especially in regions with high heat conditions. Although Wolbachia-infected mosquitoes have been rolled out in different countries such as Brazil, Colombia in South America; Indonesia, Taiwan, Viet Nam, Thailand, Malaysia, India in South Asia; Northern Queensland in Australia; and the United States of America, there is arguably no deployment yet made in Africa.
Variable effects of transient Wolbachia infections on alphaviruses in Aedes aegypti
33429Brittany L. Dodson, Sujit Pujhari, et al., PLoS Neglected Tropical Diseases, 2024-11-05 11:32:58.
Wolbachia pipientis (= Wolbachia) has promise as a tool to suppress virus transmission by Aedes aegypti mosquitoes. However, Wolbachia can have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects of Wolbachia on diverse pathogens could have important implications for public health. Here, we examine the effects of transient somatic infection with two strains of Wolbachia (wAlbB and wMel) on the alphaviruses Sindbis virus (SINV), O’nyong-nyong virus (ONNV), and Mayaro virus (MAYV) in Ae. aegypti. We found variable effects of Wolbachia including enhancement and suppression of viral infections, with some effects depending on Wolbachia strain. Both wAlbB- and wMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, with wAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects of Wolbachia were observed. The effects of Wolbachia on MAYV infections were strikingly strain-specific; wMel strongly blocked MAYV infections and suppressed viral titers, while wAlbB had more modest effects. The variable effects of Wolbachia on vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit.
Man Vs. Mosquito
33147Aman Vora, Brown Political Review, 2024-10-31 08:49:52.
It is a middle school math teacher’s favorite trivia question: What is the world’s deadliest animal? After images of a hunting tiger or towering gorilla flash through our imagination, we remember that it is the humble mosquito, whose terrible impact on human lives and healthcare systems is only projected to grow. As carbon emissions continue to rise with no plateau in sight, one oft-forgotten implication of increasing global temperatures is the devastating impact they will wreak on public health, with historically ignored diseases now able to thrive in a new, warmer climate. As global temperatures barrel toward the preferred range for mosquitoes, the number of individuals at risk for contracting malaria and dengue fever may increase by four to seven billion by 2070 relative to 1999. This threat is already a reality. Take dengue, for example: From 1980 to 1989, there were 1.5 million reported cases globally. Compare that to 2019 alone, when 5.2 million cases were reported. World Health Organization (WHO) officials described this astronomical rise in dengue as a “canary in the coalmine of the climate crisis.” No longer will mosquito-borne diseases primarily threaten equatorial regions—northern cities globally are all at risk due to the rise of Aegypti and Anopheles mosquitoes. Science: 0. Mosquitoes: 1. From bed nets to insecticides, progress is being made to combat this terrifying rise. But the current generation of anti-mosquito tools is not aggressive enough to mitigate this deadly problem: Bed nets do little to stop Aegypti, which primarily feed on blood during the day, and toxic insecticides have done little but harm the environment and drive mosquito resistance. In order to save lives from this man-made and mosquito-driven catastrophe, humanity must embrace its most promising scientific technologies: genetic engineering and Wolbachia bacteria, conscious that we are fighting against both Mother Nature and human nature itself.
Wolbachia Invasion in Mosquitoes with Incomplete CI, Imperfect Maternal Transmission and Maturation Delay
32710Ma X, Su Y, Bulletin of Mathematical Biology, 2024-10-22 17:32:46.
The mechanism of cytoplasmic incompatibility (CI) is important in the study of Wolbachia invasion in wild mosquitoes. Su et al. (Bull Math Biol 84(9):95, 2022) proposed a delay differential equation model by relating the CI effect to maturation delay. In this paper, we investigate the dynamics of this model by allowing the same density-dependent death rate and distinct density-independent death rates. Through analyzing the existence and stability of equilibria, we obtain the parameter conditions for Wolbachia successful invasion if the maternal transmission is perfect. While if the maternal transmission is imperfect, we give the ranges of parameters to ensure failure invasion, successful invasion and partially suppressing, respectively. Meanwhile, numerical simulations indicate that the system may exhibit monostable and bistable dynamics when parameters vary. Particularly, in the bistable situation an unstable separatrix, like a line, exists when choosing constant functions as initial values; and the maturation delay affects this separatrix in an interesting way.
Wolbachia-based emerging strategies for control of vector-transmitted disease
32708Diego Montenegro, Gerardo Cortés-Cortés, María Guadalupe Balbuena-Alonso, et al., Acta Tropica, 260. 2024-10-22 17:28:54.
Dengue fever is a mosquito-transmitted disease of great public health importance. Dengue lacks adequate vaccine protection and insecticide-based methods of mosquito control are proving increasingly ineffective. Here we review the emerging use of mosquitoes transinfected with the obligate intracellular bacterium Wolbachia pipientis for vector control. Wolbachia often induces cytoplasmic incompatibility in its mosquito hosts, resulting in infertile progeny between an infected male and an uninfected female. Wolbachia infection also suppresses the replication of pathogens in the mosquito, a process known as “pathogen blocking”. Two strategies have emerged. The first one releases Wolbachia carriers (both male and female) to replace the wild mosquito population, a process driven by cytoplasmic incompatibility and that becomes irreversible once a threshold is reached. This suppresses disease transmission mainly by pathogen blocking and frequently requires a single intervention. The second strategy floods the field population with an exclusively male population of Wolbachia-carrying mosquitoes to generate infertile hybrid progeny. In this case, transmission suppression depends largely on decreasing the population density of mosquitoes driven by infertility and requires continued mosquito release. The efficacy of both Wolbachia-based approaches has been conclusively demonstrated by randomized and non-randomized studies of deployments across the world. However, results conducted in one setting cannot be directly or easily extrapolated to other settings because dengue incidence is highly affected by the conditions into which the mosquitoes are released. Compared to traditional vector control methods, Wolbachia-based approaches are much more environmentally friendly and can be effective in the medium/long term. On the flip side, they are much more complex and cost-intensive operations, requiring a substantial investment, infrastructure, trained personnel, coordination between agencies, and community engagement. Finally, we discuss recent evidence suggesting that the release of Wolbachia-transinfected mosquitoes has a moderate potential risk of spreading potentially dangerous genes in the environment.
Evaluation of Wolbachia infection in Aedes aegypti suggests low prevalence and highly heterogeneous distribution in Medellín, Colombia
32509rley Calle-Tobón, Raúl Rojo-Ospina, et al., Acta Tropica, 260. 2024-10-08 09:19:14.
Dengue virus, transmitted mainly by Aedes aegypti mosquitoes, is a significant public health challenge in tropical and subtropical countries, with an incidence that is growing at an alarming rate. The release of Wolbachia-carrying mosquitoes has been suggested as a strategy to reduce the incidence of multiple arboviruses. In Medellín, Colombia, large-scale releases of Wolbachia-infected Ae. aegypti mosquitoes were performed between 2017 and 2022 by the World Mosquito Program to facilitate population replacement. In this study, we evaluated the prevalence and distribution of Wolbachia-infected Ae. aegypti two years after completion of these releases. We conducted the sampling across 19 communes in Medellín, using 416 ovitraps to collect Ae. aegypti eggs from epidemiological weeks 26 to 41 in 2023. Upon hatching the collected eggs, we identified and pooled adult female Ae. aegypti for DNA extraction. Subsequently, we conducted PCR assays for the detection of Wolbachia infection in these mosquitoes. We used maximum likelihood estimation (MLE) and Bayesian methods to estimate the prevalence of Wolbachia infection, while using QGIS to analyze spatial distribution of infection in the region. A total of 774 female Ae. aegypti mosquitoes from 182 pools were evaluated. We detected Wolbachia in 33.5 % of pools, with an estimated individual minimum infection rate of 9.5 % and a maximum of 33.2 %. The prevalence varied significantly across communes, with the highest rates observed in the northeastern and southwestern areas. Spatial analysis revealed a highly heterogeneous island-like distribution of Wolbachia across Medellín with a few hotspots. The observed Wolbachia prevalence in this work was lower than previously reported. We suspect a decline in the prevalence of Wolbachia-infected Ae. aegypti mosquitoes in Medellín following the completion of their release.
Gene Drive and Symbiont Technologies for Control of Mosquito-Borne Diseases
32504Guan-Hong Wang, Ary Hoffmann, and Jackson Champer, Annual Review of Entomology, 70. 2024-10-08 09:05:08.
Mosquito-borne diseases, such as dengue and malaria, pose a significant burden to global health. Current control strategies with insecticides are only moderately effective. Scalable solutions are needed to reduce the transmission risk of these diseases. Symbionts and genome engineering–based mosquito control strategies have been proposed to address these problems. Bacterial, fungal, and viral symbionts affect mosquito reproduction, reduce mosquito lifespan, and block pathogen transmission. Field tests of endosymbiont Wolbachia-based methods have yielded promising results, but there are hurdles to overcome due to the large-scale rearing and accurate sex sorting required for Wolbachia-based suppression approaches and the ecological impediments to Wolbachia invasion in replacement approaches. Genome engineering–based methods, in which mosquitoes are genetically altered for the modification or suppression of wild populations, offer an additional approach for control of mosquito-borne diseases. In particular, the use of gene drive alleles that bias inheritance in their favor is a potentially powerful approach. Several drives are frequency dependent, potentially giving them broadly similar population dynamics to Wolbachia. However, public acceptance and the behavior of released drives in natural mosquito populations remain challenges. We summarize the latest developments and discuss the knowledge gaps in both symbiont- and gene drive–based methods.
Wolbachia infection in Aedes aegypti does not affect its vectorial capacity for Dirofilaria immitis
32124Shirozu, T., Regilme, M.A.F., Ote, M. et al., Scientific Reports, 14. 2024-10-03 09:25:30.
Mosquito-borne diseases such as dengue and filariasis are a growing public health concern in endemic countries. Biological approaches, such as the trans-infection of Wolbachia pipientis in mosquitoes, are an alternative vector control strategy, especially for arthropod-borne viruses such as dengue. In the present study, the effect of Wolbachia (wMel strain) on the vectorial capacity of Aedes aegypti for Dirofilaria immitis was studied. Our results showed that Wolbachia does not affect the phenotype of mosquito survival or the prevalence, number, and molting rate of third-stage larvae in both susceptible and resistant strains of Ae. aegypti. RNA-seq analysis of Malpighian tubules at 2 days post-infection with D. immitis showed the differentially expressed genes (DEGs) with and without wMel infection. No characteristic immune-related gene expression patterns were observed among the DEGs. No significant change in the amount of Wolbachia was observed in the Ae. aegypti after D. immitis infection. Our results suggest that infection of D. immitis in Ae. aegypti populations will not interfere with Wolbachia-based vector control strategies in dengue-endemic areas where cases of D. immitis are present. This study demonstrated the veterinary medical validity of a dengue control program using Wolbachia.
Stable introduction of Wolbachia wPip into invasive Anopheles stephensi for potential malaria control
32022Yongkang Liang, Julian Liu, et al., PLoS Neglected Tropical Diseases, 2024-10-01 16:23:02.
Recent efforts have successfully utilized the endosymbiotic bacterium Wolbachia to control mosquito-transmitted viral diseases like dengue in multiple countries. However, similar initiatives have been limited in combating malaria, the most devastating and deadly mosquito-borne disease, which claims over half a million lives each year. This is primarily due to the difficulty in establishing a stable, maternally inheritable Wolbachia infection in Anopheles, the mosquito vector responsible for malaria transmission. A significant concern in malaria control is the invasion of the urban malaria vector Anopheles stephensi into Africa, where malaria burden is highest, and over 40% of the population resides in urban areas. Building on the previous breakthrough of establishing Wolbachia strain wAlbB in An. stephensi, the author has now achieved a second stable infection by transferring the wPip strain from Culex pipiens into this mosquito species using embryonic microinjection. The resultant transinfected HP1 line induces nearly complete cytoplasmic incompatibility when crossed with wild mosquitoes, displays robust fitness and male mating competitiveness, and exhibits strong resilience against heat stress. These advantageous traits position the HP1 line as a promising candidate for further development in malaria control.
Effectiveness of Wolbachia-mediated sterility coupled with sterile insect technique to suppress adult Aedes aegypti populations in Singapore: a synthetic control study
31580Bansal, Somya, et al., The Lancet Planetary Health, 8:617-628. 2024-09-17 10:04:54.
In this synthetic control study, we conducted a large-scale, field trial of IIT-SIT targeting Aedes aegypti among high-rise public housing estates in Singapore, an equatorial city state. Routinely collected data from a large, nationwide surveillance system of 57 990 unique mosquito traps, combined with a high-dimensional set of anthropogenic and environmental confounders were collected to ascertain mosquito abundance and its key drivers. Four townships were selected as the intervention groups (approximate population size of 607 872 residents as of 2022), wherein interventions that combined ITT with SIT over the course of the study period were conducted. Townships were subject to releases of wAlbB-SG male A aegypti mosquitoes twice a week. Data were assessed over the course of epidemiological weeks (EWs), which provide the finest temporal resolution of recorded Wolbachia release schedule and mosquito abundance data. A novel synthetic control framework was then developed to account for the non-randomised and staggered adoption setting of the intervention across trial sectors to identify the direct suppressive effectiveness of IIT-SIT on female A aegypti populations, the spillover effects in non-release areas, and the effect of the intervention on other mosquito populations such as Aedes albopictus. Furthermore, we recalculated effectiveness in terms of calendar time, time since intervention, and over multiple sites to examine heterogeneities in IIT-SIT effectiveness. Between EW27 2018 and EW26 2022, Wolbachia releases were conducted across 117 sectors, of which 97 had sufficient trap data, which were collected between EW8 2019 and EW26 2022. We found that Wolbachia-based IIT-SIT reduced wild-type female A aegypti populations by a mean of 62·01% (95% CI 60·68 to 63·26) by 3 months, 78·40% (77·56 to 79·18) by 6 months, and 91·32% (90·95 to 91·66) by at least 18 months of releases. We also found a smaller but non-negligible spillover suppression effect that gradually increased over time (mean spillover intervention effectiveness 61·02% [95% CI 57·89 to 63·72] in adjacent, non-intervention sectors). Although no consistent change in A albopictus populations was seen across the four intervention townships after Wolbachia releases, the average intervention effectiveness on the A albopictus population across all release sectors was –25·80% (95% CI –30·93 to –21·05), which was driven by increases in two towns.
Bunyamwera Virus Infection of Wolbachia-Carrying Aedes aegypti Mosquitoes Reduces Wolbachia Density
31318Lefteri, D.A.; Rainey, S.M.; Murdochy, S.M.; Sinkins, S.P., Viruses, 16. 2024-09-03 15:42:46.
Wolbachia symbionts introduced into Aedes mosquitoes provide a highly effective dengue virus transmission control strategy, increasingly utilised in many countries in an attempt to reduce disease burden. Whilst highly effective against dengue and other positive-sense RNA viruses, it remains unclear how effective Wolbachia is against negative-sense RNA viruses. Therefore, the effect of Wolbachia on Bunyamwera virus (BUNV) infection in Aedes aegypti was investigated using wMel and wAlbB, two strains currently used in Wolbachia releases for dengue control, as well as wAu, a strain that typically persists at a high density and is an extremely efficient blocker of positive-sense viruses. Wolbachia was found to reduce BUNV infection in vitro but not in vivo. Instead, BUNV caused significant impacts on density of all three Wolbachia strains following infection of Ae. aegypti mosquitoes. The ability of Wolbachia to successfully persist within the mosquito and block virus transmission is partially dependent on its intracellular density. However, reduction in Wolbachia density was not observed in offspring of infected mothers. This could be due in part to a lack of transovarial transmission of BUNV observed. The results highlight the importance of understanding the complex interactions between multiple arboviruses, mosquitoes and Wolbachia in natural environments, the impact this can have on maintaining protection against diseases, and the necessity for monitoring Wolbachia prevalence at release sites.
Excess Lipids Keep Dengue at Bay
31315Shelby Bradford, The Scientist, 2024-09-03 15:36:36.
The Aedes aegypti mosquito can transmit dengue virus; however, infection with endosymbiotic bacteria from the Wolbachia genus reduces viral transmission from these insects. Consequently, Wolbachia-infected mosquitos are one biocontrol agent used in areas with endemic dengue cases. “We are trying to go backwards now, because the intervention works, but we don’t know how,” said Robson Loterio, a microbiologist at the Burnet Institute and author of a paper published in mBio exploring the mechanism of Wolbachia’s antiviral activity. The findings can help researchers prevent viral escape from this biocontrol method. Loterio and his team infected A. aegypti cells with antiviral Wolbachia strains. Using transmission electron microscopy and confocal microscopy, they showed that these bacteria predominantly clustered at the cell’s endoplasmic reticulum (ER). The ER produces molecules used in lipid droplet synthesis. Since both Wolbachia and dengue rely on lipid metabolism, the team investigated the effect of Wolbachia on droplet formation during viral infection by comparing antiviral Wolbachia-infected cells to Wolbachia-free cells. Lipid droplets accumulated in both types of cells, but cells with the bacteria had more lipid accumulation.
A comprehensive review of Wolbachia-mediated mechanisms to control dengue virus transmission in Aedes aegypti through innate immune pathways
31172Iqra Mushtaq, Muhammad Sajjad Sarwar, Iqra Munzoor, Viral Immunology, 15. 2024-08-25 20:04:21.
The Dengue virus (DENV), primarily spread by Aedes aegypti and also by Aedes albopictus in some regions, poses significant global health risks. Alternative techniques are urgently needed because the current control mechanisms are insufficient to reduce the transmission of DENV. Introducing Wolbachia pipientis into Ae. aegypti inhibits DENV transmission, however, the underlying mechanisms are still poorly understood. Innate immune effector upregulation, the regulation of autophagy, and intracellular competition between Wolbachia and DENV for lipids are among the theories for the mechanism of inhibition. Furthermore, mainly three immune pathways Toll, IMD, and JAK/STAT are involved in the host for the suppression of the virus. These pathways are activated by Wolbachia and DENV in the host and are responsible for the upregulation and downregulation of many genes in mosquitoes, which ultimately reduces the titer of the DENV in the host. The functioning of these immune pathways depends upon the Wolbachia, host, and virus interaction. Here, we summarize the current understanding of DENV recognition by the Ae. aegypti’s immune system, aiming to create a comprehensive picture of our knowledge. Additionally, we investigated how Wolbachia regulates the activation of multiple genes associated with immune priming for the reduction of DENV.
Genetically Modified Wolbachia mosquitoes help reduce virus transmission
31461Precision Vaccinations, 2024-08-20 10:33:21.
Every year on World Mosquito Day, diseases spread by mosquitoes, which account for over 17% of all infectious diseases and lead to more than 700,000 deaths annually, are highlighted. Parasites, bacteria, or viruses can cause these diseases, including chikungunya, malaria, dengue, Zika, and yellow fever. While some diseases can be prevented with innovative travel vaccines, some can not. This is why the World Mosquito Program exists today. According to the World Mosquito Program, the Wolbachia method is vital in fighting mosquito-borne diseases and protecting communities worldwide. This program can reduce the number of Aedes aegypti mosquitoes. When male Ae. aegypti mosquitoes with Wolbachia mate with wild female mosquitoes that do not have Wolbachia. The eggs will not hatch. Because the eggs don't hatch, the number of Ae. aegypti mosquitoes decreases. They do this by breeding with wild mosquitoes until, over several generations, they replace the local mosquito population. This means Wolbachia mosquitoes help decrease the risk of dengue, Zika, chikungunya, and yellow fever outbreaks. The World Mosquito Program is currently operating in 13 countries—Australia, Brazil, Colombia, Indonesia, Sri Lanka, Honduras, Laos, Vietnam, Kiribati, Fiji, Vanuatu, New Caledonia, and Mexico—and protects more than 11.4 million people. In the United States, communities in Texas, Florida, and California have released mosquitoes with Wolbachia over the past seven years and a significant decrease in Ae. aegypti mosquitoes have been reported. In 2023, the state of Hawaiʻi also launched a Wolbachia program. Most importantly, the U.S. CDC says no data suggests that Wolbachia bacteria harm people, animals, or the environment. Let's hope locally-acquired chikungunya, dengue, and malaria cases soon become distant memories as disease-carrying mosquitos disappear.
Mosquitoes On The Run Due To Wolbachia Programmes.
30949Anonymous, St Kitts and Nevis Observer, 2024-07-25 18:53:51.
Dengue is becoming an increasingly common disease in Central America and the Caribbean, according to PAHO, even as deaths from the mosquito-born condition have fallen in recent years due to improved identification of the condition and medical care. However the World Mosquito Progam is reporting considerable success in reducing mosquito born diseases like Dengue and reporting remarkable results from countries such as Colombia and El Salvador by using something called the Wolbachia method. What is this? Wolbachia are safe, naturally occurring bacteria present in up to 50% of species, including some mosquitoes. Wolbachia has evolved to live inside the cells of many insect species. It has maintained this lifestyle for tens of thousands of years. Wolbachia cannot survive outside of insect cells because it does not have the necessary machinery to replicate itself without help from the insect host. This means Wolbachia cannot survive in the environment (e.g. the air or soil). Wolbachia is not a virus or a parasite. It is not a “gene drive”. Wolbachia has never been genetically modified by scientists. However, Wolbachia is not usually found in the Aedes aegypti mosquito, the primary species responsible for transmitting viruses such as dengue, Zika, chikungunya and epidemic yellow fever.
Incompatible insect technique: insights on potential outcomes of releasing contaminant females: a proof of concept under semi-field conditions
30947Giulia Lombardi, Elena Lampazzi, Maurizio Calvitti, Pest Management Science, 2024-07-25 18:45:37.
Releasing large numbers of Aedes albopictus males, carrying the artificially introduced Wolbachia ‘wPip’ strain, results in a decrease in the reproductive capacity of wild females due to a phenomenon known as cytoplasmic incompatibility (CI). This vector control strategy is referred to as the incompatible insect technique (IIT). However, its widespread implementation faces various challenges, including the complexity of removing fertile females from the males intended for release. Here, we present the results of semi-field experiments comparing the impact of minimal female co-release on two IIT modes: unidirectional CI-based (UnCI IIT) and bidirectional CI-based (BiCI IIT), specifically targeting Ae. albopictus. The contamination of ‘wPip’ infected females (2%) during male releases significantly weakened the overall effectiveness of IIT, emphasizing the need for thorough sex separation. Specifically, with UnCI IIT, despite the low rate of co-released females, there was a gradual rise in ‘wPip’ infection frequency, resulting in more compatible mating and subsequently higher rates of egg hatching. Conversely, this pattern was effectively mitigated in BiCI IIT owing to the reciprocal sterility between the wild-type and the ‘wPip’ infected populations. Through an experimental approach, conducted in a semi-field setting, we have contributed to advancing scientific understanding regarding the potential outcomes of implementing the IIT strategy in the absence of a complete sexing system. The results suggest that safety measures for mitigating the potential impacts of co-released females can be tailored according to the specific type of IIT being utilized. © 2024 Society of Chemical Industry.
Wolbachia endosymbionts in Drosophila regulate the resistance to Zika virus infection in a sex dependent manner
30938Ghada Tafesh-Edwards, Margarita Kyza Karaviot, Klea Markollari, et al, Frontiers in Microbiology, 15. 2024-07-24 16:02:48.
Drosophila melanogaster has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown that the presence of Wolbachia endosymbionts in D. melanogaster confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen that has recently expanded its range due to the wide geographical distribution of the mosquito vector. Here, we describe the effect of Wolbachia on the immune response of D. melanogaster adult flies following Zika virus infection. First, we show that the presence of Wolbachia endosymbionts promotes the longevity of uninfected D. melanogaster wild type adults and increases the survival response of flies following Zika virus injection. We find that the latter effect is more pronounced in females rather than in males. Then, we show that the presence of Wolbachia regulates Zika virus replication during Zika virus infection of female flies. In addition, we demonstrate that the antimicrobial peptide-encoding gene Drosocin and the sole Jun N-terminal kinase-specific MAPK phosphatase Puckered are upregulated in female adult flies, whereas the immune and stress response gene TotM is upregulated in male individuals. Finally, we find that the activity of RNA interference and Toll signaling remain unaffected in Zika virus-infected female and male adults containing Wolbachia compared to flies lacking the endosymbionts. Our results reveal that Wolbachia endosymbionts in D. melanogaster affect innate immune signaling activity in a sex-specific manner, which in turn influences host resistance to Zika virus infection. This information contributes to a better understanding of the complex interrelationship between insects, their endosymbiotic bacteria, and viral infection. Interpreting these processes will help us design more effective approaches for controlling insect vectors of infectious disease.
Culex-Transmitted Diseases: Mechanisms, Impact, and Future Control Strategies using Wolbachia
31030Madhav, M.; Blasdell, K.R.; Trewin, B.; Paradkar, P.N.; López-Denman, A.J., Viruses, 16:1134. 2024-07-15 11:40:32.
Mosquitoes of the Culex genus are responsible for a large burden of zoonotic virus transmission globally. Collectively, they play a significant role in the transmission of medically significant diseases such as Japanese encephalitis virus and West Nile virus. Climate change, global trade, habitat transformation and increased urbanisation are leading to the establishment of Culex mosquitoes in new geographical regions. These novel mosquito incursions are intensifying concerns about the emergence of Culex-transmitted diseases and outbreaks in previously unaffected areas. New mosquito control methods are currently being developed and deployed globally. Understanding the complex interaction between pathogens and mosquitoes is essential for developing new control strategies for Culex species mosquitoes. This article reviews the role of Culex mosquitos as vectors of zoonotic disease, discussing the transmission of viruses across different species, and the potential use of Wolbachia technologies to control disease spread. By leveraging the insights gained from recent successful field trials of Wolbachia against Aedes-borne diseases, we comprehensively discuss the feasibility of using this technique to control Culex mosquitoes and the potential for the development of next generational Wolbachia-based control methods.
Revisiting Wolbachia detections: Old and new issues in Aedes aegypti mosquitoes and other insects
30882Perran A. Ross, Ary A. Hoffmann, Ecology and Evolution, 14. 2024-07-07 21:12:05.
Wolbachia continue to be reported in species previously thought to lack them, particularly Aedes aegypti mosquitoes. The presence of Wolbachia in this arbovirus vector is considered important because releases of mosquitoes with transinfected Wolbachia are being used around the world to suppress pathogen transmission and these efforts depend on a lack of Wolbachia in natural populations of this species. We previously assessed papers reporting Wolbachia in natural populations of Ae. aegypti and found little evidence that seemed convincing. However, since our review, more and more papers are emerging on Wolbachia detections in this species. Our purpose here is to evaluate these papers within the context of criteria we previously established but also new criteria that include the absence of releases of transinfections within the local areas being sampled which has contaminated natural populations in at least one case where novel detections have been reported. We also address the broader issue of Wolbachia detection in other insects where similar issues may arise which can affect overall estimates of this endosymbiont more generally. We note continuing shortcomings in papers purporting to find natural Wolbachia in Ae. aegypti which are applicable to other insects as well.
Simulation-based economic evaluation of the Wolbachia method in Brazil: a cost-effective strategy for dengue control
30927Ivan Ricardo Zimmermann, Ricardo Ribeiro Alves Fernandes, Márcia Gisele Santos da Costa, et al, The Lancet Regional Health - Americas, 35. 2024-06-03 15:30:09.
Dengue virus (DENV) is an arbovirus transmitted by Aedes aegypti mosquitoes, which can cause severe conditions such as hemorrhagic fever and dengue shock syndrome. These conditions are associated with adverse social, clinical, and economic consequences in Brazil. Herein, the Wolbachia mosquito replacement method is a promising dengue control strategy. We estimated the economic impact of implementing the Wolbachia mosquito replacement method in seven Brazilian cities. A mathematical microsimulation model tracked nearly 23 million inhabitants over a 20-year period, considering the transitions between five different health states (susceptible, inapparent, outpatient, hospitalised and death). Direct costs included local dengue control programs, Wolbachia implementation and dengue care. Indirect costs related to death and productivity loss, as well as disability-adjusted life-years (DALY) averted were also considered. Without Wolbachia, the model projected 1,762,688 reported dengue cases over 20 years. Implementing the Wolbachia method would avert at least 1,295,566 dengue cases, resulting in lower costs and greater effectiveness in all simulated cities. On average, for every 1000 inhabitants followed for 20 years, the Wolbachia method yielded a cost difference of USD 538,233.68 (BRL 2,691,168.40) and averted 5.56 DALYs. Net monetary benefits (NMB) were positive in all seven cities, ranging from USD 110.72 (BRL 553.59) to USD 1399.19 (BRL 6995.95) per inhabitant. Alternative scenarios have also shown a favourable return on investment with a positive benefit-cost ratio (BCR).
Wolbachia infection-responsive immune genes suppress Plasmodium falciparum infection in Anopheles stephensi
29565Vandana V, Dong S, Sheth T, Sun Q, Wen H, Maldonado A, et al., PLoS Pathogens, 20. 2024-04-25 18:04:55.
Wolbachia, a maternally transmitted symbiotic bacterium of insects, can suppress a variety of human pathogens in mosquitoes, including malaria-causing Plasmodium in the Anopheles vector. However, the mechanistic basis of Wolbachia-mediated Plasmodium suppression in mosquitoes is not well understood. In this study, we compared the midgut and carcass transcriptomes of stably infected Anopheles stephensi with Wolbachia wAlbB to uninfected mosquitoes in order to discover Wolbachia infection-responsive immune genes that may play a role in Wolbachia-mediated anti-Plasmodium activity. We show that wAlbB infection upregulates 10 putative immune genes and downregulates 14 in midguts, while it upregulates 31 putative immune genes and downregulates 15 in carcasses at 24 h after blood-fed feeding, the time at which the Plasmodium ookinetes are traversing the midgut tissue. Only a few of these regulated immune genes were also significantly differentially expressed between Wolbachia-infected and non-infected midguts and carcasses of sugar-fed mosquitoes. Silencing of the Wolbachia infection-responsive immune genes TEP 4, TEP 15, lysozyme C2, CLIPB2, CLIPB4, PGRP-LD and two novel genes (a peritrophin-44-like gene and a macro domain-encoding gene) resulted in a significantly greater permissiveness to P. falciparum infection. These results indicate that Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.
Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes
29563Jose L. Orozco-Gonzales, Antone dos Santos Benedito, Daiver Cardona-Salgado et al., Mathematical Biosciences, 372. 2024-04-25 17:59:21.
This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model’s parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures.
Bacteria found in mosquito guts could help scientists fight dengue, Zika
29548Catherine Offord, Science, 2024-04-25 17:12:41.
A team in China probing the guts of local mosquitoes has found a potential helper in the fight against two human diseases. Researchers identified a new bacterium that disables the viruses responsible for dengue and Zika before they can establish an infection in the insects. Although early stage, the work, reported this week in Science, paves the way for studying the bacterium’s effect on disease transmission in the real world. It wouldn’t be the first time a microbe is used to thwart mosquito-borne diseases. About 15 years ago, researchers discovered that a different bacterium, Wolbachia, reduces the insects’ ability to transmit dengue, among other viruses. Following successful field trials, Wolbachia is now used to help control dengue in more than a dozen countries. But an extra weapon to help control mosquito-borne diseases is welcome—especially as the insects become resistant to current insecticides. The new study is “promising,” says Nsa Dada, a vector biologist at Arizona State University who was not involved in the work. “It’s important that we explore … new tools that can complement existing control measures.” Lacking proven treatments or widely available vaccines, dengue is the most common mosquito-borne viral disease worldwide, infecting some 400 million people each year. Although most cases are mild or asymptomatic, about one in 20 people who get sick develop severe dengue, which can be fatal.
Economic optimization of Wolbachia-infected Aedes aegypti release to prevent dengue
29104Hollingsworth BD, Cho C, Vella M, Roh H, Sass J, Lloyd AL, Brown ZS., Pest Management Science, 2024-04-16 09:30:09.
Dengue virus, primarily transmitted by the Aedes aegypti mosquito, is a major public health concern affecting ≈3.83 billion people worldwide. Recent releases of Wolbachia-transinfected Ae. aegypti in several cities worldwide have shown that it can reduce dengue transmission. However, these releases are costly, and, to date, no framework has been proposed for determining economically optimal release strategies that account for both costs associated with disease risk and releases. We present a flexible stochastic dynamic programming framework for determining optimal release schedules for Wolbachia-transinfected mosquitoes that balances the cost of dengue infection with the costs of rearing and releasing transinfected mosquitoes. Using an ordinary differential equation model of Wolbachia and dengue in a hypothetical city loosely describing areas at risk of new dengue epidemics, we determined that an all-or-nothing release strategy that quickly brings Wolbachia to fixation is often the optimal solution. Based on this, we examined the optimal facility size, finding that it was inelastic with respect to the mosquito population size, with a 100% increase in population size resulting in a 50-67% increase in optimal facility size. Furthermore, we found that these results are robust to mosquito life-history parameters and are mostly determined by the mosquito population size and the fitness costs associated with Wolbachia. These results reinforce that Wolbachia-transinfected mosquitoes can reduce the cost of dengue epidemics. Furthermore, they emphasize the importance of determining the size of the target population and fitness costs associated with Wolbachia before releases occur.
Wolbachia Infection through Hybridization to Enhance an Incompatible Insect Technique-Based Suppression of Aedes albopictus in Eastern Spain
29086Cholvi M, Trelis M, Bueno-Marí R, Khoubbane M, Gil R, Marcilla A, Moretti R., Insects, 15. 2024-04-04 09:29:30.
Wolbachia bacteria occur naturally as symbionts of many insect species and are responsible for various phenomena that modify the hosts’ reproductive biology. Among them, cytoplasmic incompatibility (CI) refers to the sterility of eggs produced by crosses between infected males and females that are uninfected or infected by a non-compatible strain of these bacteria. CI can be exploited for vector control by establishing an opportune Wolbachia infection in a laboratory population of a target insect species and then releasing the infected males into the environment as sterilizing agents. In the present work, a suitable Wolbachia strain was introduced into a Spanish population of the Asian tiger mosquito, Aedes albopictus, through hybridization with the laboratory line, ARwP, already tested as an efficient control tool against this vector. The obtained hybrids were compared with the ARwP to ascertain the effects derived from transferring the infection to a different Ae. albopictus population. No significant differences between lines were found regarding survival, female fecundity, and egg fertility. Importantly, the eggs produced by crosses between males of the hybrid lines and unmodified wild females were 99.9% sterile. This result encourages further studies to explore the feasibility of a Wolbachia-based control program against the Asian tiger mosquito in Spain.
Detection and quantification of natural Wolbachia in Aedes aegypti in Metropolitan Manila, Philippines using locally designed primers
29084Reyes JIL, Suzuki T, Suzuki Y, Watanabe K., Frontiers in Cellular and Infection Microbiology, 2024-04-04 09:23:33.
The Philippines bears health and economic burden caused by high dengue cases annually. Presently, the Philippines still lack an effective and sustainable vector management. The use of Wolbachia, a maternally transmitted bacterium, that mitigate arbovirus transmission has been recommended. Cytoplasmic incompatibility and viral blocking, two characteristics that make Wolbachia suitable for vector control, depend on infection prevalence and density. There are no current Wolbachia release programs in the Philippines, and studies regarding the safety of this intervention. Here, we screened for Wolbachia in Aedes aegypti collected from Metropolitan Manila, Philippines. We designed location-specific primers for qPCR to test whether this improved Wolbachia detection in Ae. aegypti. We explored if host sex and Wolbachia strain could be potential factors affecting Wolbachia density.
Monitoring Aedes populations for arboviruses, Wolbachia, insecticide resistance and its mechanisms in various agroecosystems in Benin
29064S. Ateutchia-Ngouanet, F. Nanfack-Minkeu, K. Mavridis, S. Wanji, M. Demanou, J. Vontas, R. Djouaka, Acta Tropica, 253. 2024-04-02 11:34:55.
The susceptibility of arbovirus vectors to insecticides and the microbiome of Aedes species are understudied in Benin.
Researchers reveal how a virus hijacks insect sperm: May help control disease vectors and pests
29043Pennsylvania State University, Phys.org, 2024-03-19 17:39:54.
A new study led by researchers at Penn State has uncovered how a widespread bacteria called Wolbachia and a virus that it carries can cause sterility in male insects by hijacking their sperm.
Wolbachia strain wAlbB shows favourable characteristics for dengue control use in Aedes aegypti from Burkina Faso
29041Maria Vittoria Mancini, Shivan M. Murdochy, Etienne Bilgo, Thomas H. Ant, Daniel Gingell, Edounou Jacques Gnambani, Anna-Bella Failloux, Abdoulaye Diabate, Steven P. Sinkins, Environmental Microbiology, 26. 2024-03-19 16:46:34.
Dengue represents an increasing public health burden worldwide.
Alpha-mannosidase-2 modulates arbovirus infection in a pathogen- and Wolbachia-specific manner in Aedes aegypti mosquitoes
29035Nadya Urakova, Renuka E. Joseph, Allyn Huntsinger, Vanessa M. Macias, Matthew J. Jones, Leah T. Sigle, Ming Li, Omar S. Akbari, Zhiyong Xi, Konstantinos Lymperopoulos, Richard T. Sayre, Elizabeth A. McGraw, Jason L. Rasgon, Insect Molecular Biology, 2024-03-19 15:50:02.
Multiple Wolbachia strains can block pathogen infection, replication and/or transmission in Aedes aegypti mosquitoes under both laboratory and field conditions.
Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality
29033Rupinder Kaur et al., Science, 383:1111-1117. 2024-03-19 15:33:59.
Many arthropods carry symbiotic bacteria. Some, including Wolbachia strains, have the capacity to cause male sterility.
Comparative analysis of Wolbachia maternal transmission and localization in host ovaries
29029Michael T.J. Hague, Timothy B. Wheeler, Brandon S. Cooper, bioRxiv, 2024-03-19 13:26:24.
Acceptability of emergent Aedes aegypti vector control methods in Ponce, Puerto Rico: A qualitative assessment
29010Pérez-Guerra CL, Rosado-Santiago C, Ramos SA, Marrero-Santos KM, González-Zeno G, Partridge SK, et al., PLoS Global Public Health, 2024-03-11 13:41:04.
Aedes aegypti control has been fraught with challenges in Puerto Rico. The government has implemented commonly used vector control methods, but arboviral epidemics still occur. It is necessary to explore new Ae. aegypti control methods. This study aimed to understand the perceptions of community members in Ponce, Puerto Rico about emergent and traditional Ae. aegypti vector control methods and determine their acceptability and support for these methods. We identified the type of information needed to increase support for emergent vector control methods, and the preferred strategies to disseminate this information. Four group discussions were conducted with a total of 32 participants representing eight of the 14 clusters participating in the Communities Organized for the Prevention of Arboviruses (COPA), a project designed to mobilize communities in Ponce, Puerto Rico to prevent diseases transmitted by mosquitoes. Group discussions began with an overview of different methods used for controlling Ae. aegypti mosquitoes. These overviews facilitated participant understanding of the mosquito control methods presented. Use of source reduction, autocidal gravid ovitraps (AGO), and manual application of larvicide for arboviral mosquito control received support from almost all participants. Vector control methods that use more familiar techniques in Puerto Rico such as truck-mounted larvicide spraying (TMLS) and insecticide residual spraying received support from most participants. More than half of participants supported the use of emergent mosquito control methods including Wolbachia suppression, Wolbachia replacement, or genetically modified mosquitoes (GMM). Participants preferred to receive vector control information through house-to-house visits with the distribution of written materials, followed by dissemination of information through traditional (i.e., radio, television) and social media. The detailed information resulting from this study was used to develop messages for a communications campaign to garner future community support. Community acceptance and support are critical for the success of vector control programs using emergent mosquito control methods.
Efficacy of Wolbachia-based mosquito control: Predictions of a spatially discrete mathematical model
29008David Dye, John W. Cain, PLoS One, 19. 2024-03-11 12:43:55.
Wolbachia is an endosymbiont bacterium present in many insect species. When Wolbachia-carrying male Aedes aegypti mosquitoes mate with non-carrier females, their embryos are not viable due to cytoplasmic incompatibility. This phenomenon has been exploited successfully for the purpose of controlling mosquito populations and the spread of mosquito-borne illnesses: Wolbachia carriers are bred and released into the environment. Because Wolbachia is not harmful to humans, this method of mosquito control is regarded as a safer alternative to pesticide spraying. In this article, we introduce a mathematical framework for exploring (i) whether a one-time release of Wolbachia carriers can elicit a sustained presence of carriers near the release site, and (ii) the extent to which spatial propagation of carriers may allow them to establish fixation in other territories. While some prior studies have formulated mosquito dispersal models using advection-reaction-diffusion PDEs, the predictive power of such models requires careful ecological mapping: advection and diffusion coefficients exhibit significant spatial dependence due to heterogeneity of resources and topography. Here, we adopt a courser-grained view, regarding the environment as a network of discrete, diffusively-coupled “habitats”—distinct zones of high mosquito density such as stagnant ponds. We extend two previously published single-habitat mosquito models to multiple habitats, and calculate rates of migration between pairs of habitats using dispersal kernels. Our primary results are quantitative estimates regarding how the success of carrier fixation in one or more habitats is determined by: the number of carriers released, sizes of habitats, distances between habitats, and the rate of migration between habitats. Besides yielding sensible and potentially useful predictions regarding the success of Wolbachia-based control, our framework applies to other approaches (e.g., gene drives) and contexts beyond the realm of insect pest control.
Aedes aegypti Controls Ae. aegypti: SIT and IIT—An Overview
29003Robert L. Aldridge; Seth Gibson; Kenneth J. Linthicum, Journal of the American Mosquito Control Association, 20:32-49. 2024-03-11 12:34:19.
The sterile insect technique (SIT) and the incompatible insect technique (IIT) are emerging and potentially revolutionary tools for controlling Aedes aegypti (L.), a prominent worldwide mosquito vector threat to humans that is notoriously difficult to reduce or eliminate in intervention areas using traditional integrated vector management (IVM) approaches. Here we provide an overview of the discovery, development, and application of SIT and IIT to Ae. aegypti control, and innovations and advances in technology, including transgenics, that could elevate these techniques to a worldwide sustainable solution to Ae. aegypti when combined with other IVM practices.
DENV-1 Titer Impacts Viral Blocking in wMel Aedes aegypti with Brazilian Genetic Background
28991Corrêa-Antônio, Jessica, Mariana R. David, Dinair Couto-Lima, Gabriela Azambuja Garcia, Milan S. G. Keirsebelik, Rafael Maciel-de-Freitas, and Márcio Galvão Pavan., Viruses, 16. 2024-03-11 10:08:24.
Several countries have been using Wolbachia deployments to replace highly competent native Aedes aegypti populations with Wolbachia-carrying mosquitoes with lower susceptibility to arboviruses such as dengue, Zika, and chikungunya. In Rio de Janeiro, Wolbachia deployments started in 2015 and still present a moderate introgression with a modest reduction in dengue cases in humans (38%). Here, we evaluated the vector competence of wild-type and wMel-infected Ae. aegypti with a Brazilian genetic background to investigate whether virus leakage could contribute to the observed outcomes in Brazil. We collected the specimens in three areas of Rio de Janeiro with distinct frequencies of mosquitoes with wMel strain and two areas with wild Ae. aegypti. The mosquitoes were orally exposed to two titers of DENV-1 and the saliva of DENV-1-infected Ae. aegypti was microinjected into wMel-free mosquitoes to check their infectivity. When infected with the high DENV-1 titer, the presence of wMel did not avoid viral infection in mosquitoes’ bodies and saliva but DENV-1-infected wMel mosquitoes produced lower viral loads than wMel-free mosquitoes. On the other hand, wMel mosquitoes infected with the low DENV-1 titer were less susceptible to virus infection than wMel-free mosquitoes, although once infected, wMel and wMel-free mosquitoes exhibited similar viral loads in the body and the saliva. Our results showed viral leakage in 60% of the saliva of wMel mosquitoes with Brazilian background; thus, sustained surveillance is imperative to monitor the presence of other circulating DENV-1 strains capable of overcoming the Wolbachia blocking phenotype, enabling timely implementation of action plans.
PSRs: Selfish chromosomes that manipulate reproductive development
28974Xinmi Zhang, Patrick M. Ferree, Seminars in Cell and Developmental Biology, 159-160:66-73. 2024-03-05 14:28:18.
B chromosomes are intriguing “selfish” genetic elements, many of which exhibit higher-than-Mendelian transmission. This perspective highlights a group of B chromosomes known as Paternal Sex Ratio chromosomes (PSRs), which are found in several insects with haplo-diploid reproduction. PSRs harshly alter the organism’s reproduction to facilitate their own inheritance. A manifestation of this effect is the conversion of female destined individuals into males. Key to this conversion is the mysterious ability of PSRs to cause elimination of the sperm-inherited half of the genome during zygote formation. Here we discuss how PSRs were discovered, what is known about how they alter paternal chromatin dynamics to cause sex conversion, and how PSR-induced genome elimination is different from other forms of programmed genome elimination in different insects. PSRs also stand out because their DNA sequence compositions differ in remarkable ways from their insect’s essential chromosomes, a characteristic suggestive of interspecies origins. Broadly, we also highlight poorly understood aspects of PSR dynamics that need to be investigated.
Taking the fight against disease to mosquitoes
28948Gregory Devine, Setopati, 2024-02-27 18:33:30.
In the medium term it's likely that suppression strategies involving self-limiting genetic modifications, Wolbachia infection and irradiation will be extended to a small number of our most important mosquito vectors of disease.
Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: a synthetic control study in Singapore
28940Jue Tao Lim, Somya Bansal*, Chee Seng Chong*, Borame Dickens, Youming Ng, Lu Deng, Caleb Lee, Li Yun Tan, Grace Chain, Pei Ma, Shuzhen Sim, Cheong Huat Tan, Alex R Cook, Lee Ching Ng, The Lancet Microbe, 2024-02-27 18:18:52.
Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77·28% (121/156, 95% CI 75·81–78·58) intervention efficacy despite incomplete coverage across all towns until EW 26, 2022. Intervention efficacies increased as release coverage increased across all intervention sites. Releases led to 2242 (95% CI 2092–2391) fewer cases per 100 000 people in intervention sites during the study period. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites.
Introduction of Aedes aegypti mosquitoes carrying wAlbB Wolbachia sharply decreases dengue incidence in disease hotspots
28927AA Hoffmann, NW Ahmad, WM Keong, CY Ling, NA Ahmad, N. Golding, N. Tierney, J. Jelip, PW Putit, N Mohktar, SS Sandhu, LS Ming, et al., iScience, 2024-02-27 16:48:03.
Partial replacement of resident Aedes aegypti mosquitoes with introduced mosquitoes carrying certain strains of inherited Wolbachia symbionts can result in transmission blocking of dengue and other viruses of public health importance. Wolbachia strain wAlbB is an effective transmission blocker and stable at high temperatures, making it particularly suitable for hot tropical climates. Following trial field releases in Malaysia, releases using wAlbB Ae. aegypti have become operationalized by the Malaysian health authorities. We report here on an average reduction in dengue fever of 62.4% (confidence intervals 50–71%) in 20 releases sites when compared to 76 control sites in high-rise residential areas. Importantly the level of dengue reduction increased with Wolbachia frequency, with 75.8% reduction (61–87%) estimated at 100% Wolbachia frequency. These findings indicate large impacts of wAlbB Wolbachia invasions on dengue fever incidence in an operational setting, with incidence expected to further decrease as wider areas are invaded.
Judge sides with Hawaii to block challenge to mosquito release plan
28925Candice Cheung, Courthouse News Service, 2024-02-27 16:29:17.
A planned program to save endemic Hawaiian birds from avian malaria by releasing thousands of biopesticide mosquitoes into Maui’s rainforest will go on, despite an attempt by an environmental nonprofit to block the project.First Circuit Court Judge John Tonaki ruled Tuesday in favor of the state of Hawaii, its Department of Land and Natural Resources and conservationists to block a lawsuit claiming the state agency did not complete a proper environmental evaluation of program aimed at curbing mosquito population to prevent them from spreading avian malaria.“This is a victory for our endangered forest birds who some native Hawaiians consider their ancestors,” Dawn Chang, chair of the state’s Board of Land and Natural Resources said in a statement. “The HEPA is an important tool that enables decisionmakers to assess environmental impacts — not the sword by which misinformation kills a project, aimed at saving native species.”
South American cities release mosquitoes to stem disease
28913Roberto González, SciDev.Net, 2024-02-20 19:48:12.
When Waldeir Barbosa da Silva explained to his family that he was going to release hundreds of thousands of mosquitoes into the open, infected with a bacterium, they were surprised. In Niterói, southeast Brazil, where da Silva lives, diseases spread by mosquitoes, such as dengue, chikungunya, and Zika, pose a serious public health problem. However, when mosquitoes carry the bacteria Wolbachia, naturally present in many insects, their ability to transmit these viruses decreases.
Intra-lineage microevolution of Wolbachia leads to the emergence of new cytoplasmic incompatibility patterns
28889Namias A, Ngaku A, Makoundou P, Unal S, Sicard M, Weill M, PLoS Biology, 2024-02-13 20:25:15.
Mosquitoes of the Culex pipiens complex are worldwide vectors of arbovirus, filarial nematodes, and avian malaria agents. In these hosts, the endosymbiotic bacteria Wolbachia induce cytoplasmic incompatibility (CI), i.e., reduced embryo viability in so-called incompatible crosses. Wolbachia infecting Culex pipiens (wPip) cause CI patterns of unparalleled complexity, associated with the amplification and diversification of cidA and cidB genes, with up to 6 different gene copies described in a single wPip genome. In wPip, CI is thought to function as a toxin-antidote (TA) system where compatibility relies on having the right antidotes (CidA) in the female to bind and neutralize the male’s toxins (CidB). By repeating crosses between Culex isofemale lines over a 17 years period, we documented the emergence of a new compatibility type in real time and linked it to a change in cid genes genotype. We showed that loss of specific cidA gene copies in some wPip genomes results in a loss of compatibility. More precisely, we found that this lost antidote had an original sequence at its binding interface, corresponding to the original sequence at the toxin’s binding interface. We showed that these original cid variants are recombinant, supporting a role for recombination rather than point mutations in rapid CI evolution. These results strongly support the TA model in natura, adding to all previous data acquired with transgenes expression.
Evidence of Differences in Cellular Regulation of Wolbachia-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
28852Rainey SM, Lefteri DA, Darby C, Kohl A, Merits A, Sinkins SP., Viruses, 16(1):115. 2024-01-28 13:51:52.
The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses.
The epidemiology of imported and locally-acquired dengue in Australia, 2012–2022
28826Asma Sohail, Katherine L Anders, Sarah L McGuinness, Karin Leder, Journal of Travel Medicine, 2024-01-23 17:13:52.
Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019.
Wolbachia still works when it is warm
28809McKay, A., Nature Ecology and Evolution, 8. 2024-01-16 13:59:40.
Wolbachia is a maternally inherited endosymbiotic bacterium that can impede the transmission of viruses such as dengue and Zika by some mosquito vectors to humans. Over the past decade, this self-sustaining disease-control method has been rolled out in cities of increasing size; 2023 saw the largest demonstration of efficacy to date, in Medellín, Colombia. However, two key biological mechanisms that enable Wolbachia-carrying mosquitoes to spread in a population — cytoplasmic incompatibility and maternal transmission — have been shown in laboratory conditions to decline under high temperatures. Writing in Nature Climate Change in August 2023, Vásquez and colleagues conducted computational simulations to explore whether near-future warming scenarios are likely to affect the efficacy of Wolbachia-based biocontrol. The models combine empirical estimates of thermal sensitivity for one strain of Wolbachia with projections of future average temperatures and heatwaves for Cairns, Australia and Nha Trang City, Vietnam, two locations where the intervention has been deployed. Estimates of the bacterium’s successful persistence in the mosquito population remain high under tested projections of moderate and severe average warming to 2050. However, the simulations also show reduced efficacy under more variable thermal extremes; these interventions have the potential to fail under extreme warming with long heatwave durations. We selected this paper for our Year in Review collection because it exemplifies how insect thermal biology and global change analysis can offer insights relevant to human health. Testing whether climate change influences Wolbachia-based biocontrol helps to illuminate whether the promising technology is likely to remain feasible in coming years.
Limited association between Wolbachia and Plasmodium falciparum infections in natural populations of the major malaria mosquito Anopheles moucheti
28760Théo Mouillaud, Audric Berger, Marie Buysse, Nil Rahola, Josquin Daron, Jean-Pierre Agbor, Sandrine N. Sango, Daniel E. Neafsey, Olivier Duron, Diego Ayala, Evolutionary Applications, 16:1999-2006. 2024-01-07 16:47:29.
Since the discovery of natural malaria vector populations infected by the endosymbiont bacterium Wolbachia, a renewed interest has arisen for using this bacterium as an alternative for malaria control. Among naturally infected mosquitoes, Anopheles moucheti, a major malaria mosquito in Central Africa, exhibits one of the highest prevalences of Wolbachia infection. To better understand whether this maternally inherited bacterium could be used for malaria control, we investigated Wolbachia influence in An. moucheti populations naturally infected by the malaria parasite Plasmodium falciparum. To this end, we collected mosquitoes in a village from Cameroon, Central Africa, where this mosquito is the main malaria vector. We found that the prevalence of Wolbachia bacterium was almost fixed in the studied mosquito population, and was higher than previously recorded. We also quantified Wolbachia in whole mosquitoes and dissected abdomens, confirming that the bacterium is also elsewhere than in the abdomen, but at lower density. Finally, we analyzed the association of Wolbachia presence and density on P. falciparum infection. Wolbachia density was slightly higher in mosquitoes infected with the malaria parasite than in uninfected mosquitoes. However, we observed no correlation between the P. falciparum and Wolbachia densities. In conclusion, our study indicates that naturally occurring Wolbachia infection is not associated to P. falciparum development within An. moucheti mosquitoes.
Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication
28757Robson K. Loterio, Ebony A. Monson, Rachel Templin, Jyotika T. de Bruyne, Heather A. Flores, Jason M. Mackenzie, Georg Ramm, Karla J. Helbig, Cameron P. Simmons, Johanna E. Fraser, Applied and Environmental Microbiology, 2023-12-22 16:16:14.
Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to reduce the incidence of Aedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinning the antiviral activity of these Wolbachia strains are not well defined. Here, we generated a panel of Ae. aegypti-derived cell lines infected with antiviral strains wMel and wAlbB or the non-antiviral Wolbachia strain wPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied by wMel. Together, this suggests that antiviral Wolbachia strains may specifically alter the lipid composition of the ER to preclude the establishment of dengue virus (DENV) replication complexes. Defining Wolbachia’s antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.
Wolbachia infection negatively impacts Drosophila simulans heat tolerance in a strain- and trait-specific manner
28736Liam F Ferguson, Perran A Ross, Belinda van Heerwaarden, bioRxiv, 2023-12-19 16:09:01.
The susceptibility of insects to rising temperatures has largely been measured by their ability to survive thermal extremes. However, until recently, the capacity for maternally inherited endosymbionts to influence insect heat tolerance has been overlooked. Further, the impact of heat on traits like fertility, which can decline at temperatures below the lethal thermal limit has largely been ignored. Here, we assess the impact of three Wolbachia strains (wRi, wAu, and wNo) on the survival and fertility of Drosophila simulans exposed to heat stress during development or as adults. The impact of Wolbachia infection on heat tolerance was generally small and trait/strain specific. Only the wNo infection significantly reduced survival and fertility of adult males after a heat shock. When exposed to a fluctuating heat stress during development, the wRi and wAu strains reduced egg-to-adult survival but only the wNo infection reduced male fertility. Wolbachia densities of all three strains decreased under developmental heat stress, but reductions occurred at temperatures above those that reduced fertility of the host. These findings reveal the complexity of endosymbiont-host-environment interactions and emphasise the necessity to account for endosymbionts and their effect on both survival and fertility when investigating the vulnerability of insects to climate change.
Rapid turnover of pathogen-blocking Wolbachia and their incompatibility loci
28733Shropshire JD, Conner WR, Vanderpool D, Hoffmann AA, Turelli M, Cooper BS., bioRxiv, 2023-12-19 16:02:29.
At least half of all insect species carry maternally inherited Wolbachia alphaproteobacteria, making Wolbachia the most common endosymbionts in nature. Wolbachia spread to high frequencies is often due to cytoplasmic incompatibility (CI), a Wolbachia -induced sperm modification that kills embryos without Wolbachia . Several CI-causing Wolbachia variants, including w Mel from Drosophila melanogaster , also block viruses. Establishing pathogen-blocking w Mel in natural Aedes aegypti mosquito populations has reduced dengue disease incidence, with one study reporting about 85% reduction when w Mel frequency is high. However, w Mel transinfection establishment is challenging in many environments, highlighting the importance of identifying CI-causing Wolbachia variants that stably persist in diverse hosts and habitats. We demonstrate that w Mel-like variants have naturally established in widely distributed holometabolous dipteran and hymenopteran insects that diverged approximately 350 million years ago, with w Mel variants spreading rapidly among these hosts over only the last 100,000 years. Wolbachia genomes contain prophages that encode CI-causing operons ( cifs ). These cifs move among Wolbachia genomes - with and without prophages - even more rapidly than Wolbachia move among insect hosts. Our results shed light on how rapid host switching and horizontal gene transfer contribute to Wolbachia and cif diversity in nature. The diverse w Mel variants we report here from hosts present in different climates offer many new options for broadening Wolbachia -based biocontrol of diseases and pests.
Procesos celulares modificados en Aedes aegypti infectados con Wolbachia y la susceptibilidad al virus dengue
28696López-Ordóñez T, Díaz-Rodarte KI, Torres-Monzón JA, Casas-Martínez M, Danis-Lozano R, Mosso-González C., Salud Pública de México, 2023-12-12 14:35:34.
Objetivo: Analizar la expresión diferencial de proteínas de Aedes aegypti infectados con Wolbachia y su asociación con el ciclo viral del virus dengue (DENV). Material y métodos. Se revisó una base de datos de proteínas de Ae. aegypti infec-tados y no infectados con Wolbachia, cepa wMel y se buscaron estas en revistas indizadas, que hablaran de la proteína y el ciclo viral de DENV. Resultados: La expresión diferencial de proteínas de los mosquitos durante la infección con Wolbachia intervienen en los procesos de entrada, replicación y salida del DENV. Conclusiones: Existen cambios en la expresión de proteínas de células infectadas con Wolbachia, que son necesarias para el ciclo de replicación de DENV, explicando porque algunos mosquitos infectados con Wolbachia son refractarios a la infección por DENV.
The effect of migration on transmission of Wolbachia in Nilaparvata lugens
28679Zhigang Liu, Tiejun Zhou, Mathematical Biosciences and Engineering, 20. 2023-12-06 13:40:37.
Brown planthopper Nilaparvata lugens, which can transmit rice ragged stunt virus, is a serious and damaging pest to rice plants. Rice plants can protect themselves from the associated diseases of N.lugens by either suppressing or replacing N.lugens by releasing N.lugens infected by a special strain of Wolbachia wStri. The long-distance migration habit of N.lugens is one of the important precursors leading up to the large-scale occurrence of N.lugens. To study the effect of migration on the transmission of Wolbachia in N.lugens, a Wolbachia spreading dynamics model with migration of N.lugens between two patches is put forward. The existence and local stability conditions of equilibrium points of the system and its subsystems are obtained. Moreover, the effects of migration on the dynamic properties and the control of N.lugens are analyzed; the results show that the system can exhibit a bistable phenomenon, and the migration can change the stability of equilibrium infected with wStri from stable to unstable. The quantitative control methods for the migration of the insect N.lugens are proposed, which provide a theoretical guidance for future field experiments. Lastly, we use the Markov chain Monte Carlo (MCMC) method to estimate the parameters of the wild N.lugens migration model based on limited observational data; the numerical simulation results show that migration can increase the quantity of N.lugens, which is consistent with the relevant experimental results.
Reduced dengue incidence following city-wide wMel Wolbachia mosquito releases throughout three Colombian cities: Interrupted time series analysis and a prospective case-control study
28647Velez ID, Tanamas SK, Arbelaez MP, Kutcher SC, Duque SL, Uribe A, et al., PLoS Neglected Tropical Diseases, 2023-12-05 10:26:43.
The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings.
Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí, Colombia
28645Velez ID, Uribe A, Barajas J, Uribe S, Ángel S, Suaza-Vasco JD, et al., PLoS Neglected Tropical Diseases, 2023-12-05 10:11:27.
The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and has been shown to reduce the transmission of dengue and other Aedes-borne viruses. Here we report the entomological results from phased, large-scale releases of Wolbachia infected Ae. aegypti mosquitoes throughout three contiguous cities located in the Aburrá Valley, Colombia. These results, from the largest contiguous releases of wMel Wolbachia mosquitoes to date, highlight the operational feasibility of implementing the method in large urban settings. Based on results from previous studies, we expect that Wolbachia establishment will be sustained long term. Ongoing monitoring will confirm Wolbachia persistence in local mosquito populations and track its establishment in the remaining areas.
Modelling and analysis of periodic impulsive releases of the Nilaparvata lugens infected with wStri-Wolbachia
28638Xiangjun Dai, Qi Quan and Jianjun Jiao, Journal of Biological Dynamics, 17:1. 2023-12-04 12:23:12.
In this paper, we formulate a population suppression model and a population replacement model with periodic impulsive releases of Nilaparvata lugens infected with wStri. The conditions for the stability of wild-N.lugens -eradication periodic solution of two systems are obtained by applying the Floquet theorem and comparison theorem. And the sufficient conditions for the persistence in the mean of wild N.lugens are also given. In addition, the sufficient conditions for the extinction and persistence of the wild N.lugens in the subsystem without wLug are also obtained. Finally, we give numerical analysis which shows that increasing the release amount or decreasing the release period are beneficial for controlling the wild N.lugens, and the efficiency of population replacement strategy in controlling wild populations is higher than that of population suppression strategy under the same release conditions.
Wolbachia Transinfection Via Embryonic Microinjection
28593Zhang, M., Xi, Z., Methods in Molecular Biology, 2739. 2023-11-29 16:22:25.
The process of transferring Wolbachia from one species to another to establish a stable, maternally inherited infection in the target species is known as transinfection. The success of transinfection is primarily achieved through embryonic microinjection, which is the most direct and efficient means of delivering Wolbachia into the germline of the target species and establishing stable maternal transmission. For the fundamental studies, transinfection is often used to characterize Wolbachia-host interactions, including Wolbachia host range, the role of host or bacterial factors in symbiosis, and evolution of Wolbachia-host associations. For the applied studies, use of transinfection to generate a novel infection in the target species is the first step to build the weapon for both population replacement and population suppression for controlling insect pests or their transmitted diseases. For the primary dengue vector Aedes aegypti and Anopheles vectors of malaria, which either do not naturally carry Wolbachia or are infected with strains that lack necessary features for implementation, transinfection can be established by introducing a novel strain capable of inducing both cytoplasmic incompatibility (CI) and pathogen blocking. For A. albopictus and Culex mosquito species, which naturally harbor CI-inducing Wolbachia, transinfection can be achieved by either introducing a novel strain to generate superinfection or replacing the native infection with a different Wolbachia strain in a symbiont-free line, which is derived from antibiotic treatment of the wild type. Here, we use A. aegypti as an example to describe the Wolbachia transinfection method, which can be adapted to other insect species, such as planthoppers, according to their specific developmental requirements.
Measuring Host Fitness Effects and Transmission of Wolbachia Strains in Aedes aegypti Mosquitoes
28587Ross, P.A., Methods in Molecular Biology, 2739. 2023-11-29 15:49:58.
Lines of Aedes aegypti mosquitoes infected with heritable Wolbachia bacteria are being developed and released for arbovirus control. Coordinated releases of lab-reared Wolbachia mosquitoes have reduced local disease incidence by spreading virus-blocking Wolbachia strains and by crashing mosquito populations through incompatible male releases. The phenotypic effects of Wolbachia are diverse and depend on both genetics and the environment. Accurate assessments of Wolbachia effects in mosquitoes are essential, as such effects can make the difference between success and failure of a Wolbachia release program. This chapter provides guidelines for testing key Wolbachia host effects and transmission in Aedes aegypti: the most important arbovirus vector and the most common target of Wolbachia release programs. The protocols should be useful for evaluating mosquito strains prior to field release.
Procedures for the Detection of Wolbachia-Conferred Antiviral Protection in Drosophila melanogaster
28581Chrostek, E., Methods in Molecular Biology, 2739. 2023-11-29 15:34:15.
Spread of Wolbachia infections in host populations may be enhanced by Wolbachia-conferred protection from viral pathogens. Wolbachia-infected Drosophila melanogaster survive the pathogenic effects of positive-sense single-stranded RNA virus infections at a higher rate than the flies without Wolbachia. The protection can occur with or without detectable reduction in virus titer. For the comparisons to be meaningful, Wolbachia-harboring and Wolbachia-free insects need to be genetically matched, and original populations of gut microbiota need to be restored after the removal of Wolbachia using antibiotics. Here, I describe the procedures needed to detect Wolbachia-conferred antiviral protection against Drosophila C virus measured as the difference in survival and viral titer between flies with and without Wolbachia.
Use of Drosophila Transgenics to Identify Functions for Symbiont Effectors
28574Cortez, C.T., Murphy, R.O., Owens, I.M., Beckmann, J.F., Methods in Molecular Biology, 2739. 2023-11-29 14:35:56.
Wolbachia, one of the most successful and studied insect symbionts, and Drosophila, one of the most understood model insects, can be exploited as complementary tools to unravel mechanisms of insect symbiosis. Although Wolbachia itself cannot be grown axenically as clonal isolates or genetically manipulated by standard methods, its reproductive phenotypes, including cytoplasmic incompatibility (CI), have been elucidated using well-developed molecular tools and precise transgenic manipulations available for Drosophila melanogaster. Current research only scratches the surface of how Drosophila can provide a tool for understanding Wolbachia’s evolutionary success and the molecular roles of its genetic elements. Here, we briefly outline basic methodologies inherent to transgenic Drosophila systems that have already contributed significant advances in understanding CI, but may be unfamiliar to those who lack experience in Drosophila genetics. In the future, these approaches will continue providing significant insights into Wolbachia that undoubtedly will be extended to other insect symbionts and their biological capabilities.
Different mechanisms of X-ray irradiation-induced male and female sterility in Aedes aegypti
28570Zhang, H., Trueman, E., Hou, X. et al., BMC Biology, 21. 2023-11-29 14:14:21.
Aedes aegypti (Ae. aegypti) is the major vector that transmits many diseases including dengue, Zika, and filariasis in tropical and subtropical regions. Due to the growing resistance to chemical-based insecticides, biological control methods have become an emerging direction to control mosquito populations. The sterile insect technique (SIT) deploys high doses of ionizing radiation to sterilize male mosquitoes before the release. The Wolbachia-based population suppression method of the incompatible insect technique (IIT) involves the release of Wolbachia-infected males to sterilize uninfected field females. Due to the lack of perfect sex separation tools, a low percentage of female contamination is detected in the male population. To prevent the unintentional release of these Wolbachia-infected females which might result in population replacement, a low dose of X-ray irradiation is deployed to sterilize any female escapees. However, it remains unclear whether these irradiation-induced male and female sterilizations share common mechanisms.
Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
28311A. Minwuyelet, G. P. Petronio, D. Yewhalaw, A. Sciarretta, I. Magnifico, D. Nicolosi, R. Di Marco and G. Atenafu, Frontiers in Microbiology, 14. 2023-11-08 08:20:47.
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
Success of Wolbachia-infected mosquitoes in fighting dengue may be underestimated
28353B. Wampler, Notre Dame News, 2023-11-06 11:04:57.
Now, researchers at the University of Notre Dame have conducted an analysis of the World Mosquito Program’s randomized control trial of Wolbachia-infected mosquitoes in Indonesia, looking at how excluding transmission dynamics impacted the original interpretation of the trial’s results. “Randomized controlled trials are the gold standard for evaluating the efficacy of any medical or public health intervention. That is very difficult for vector interventions against dengue because incidence of the disease can be somewhat unpredictable and sporadic, requiring very large-scale trials,” said Alex Perkins, associate professor of biological sciences at Notre Dame and senior author on the study. The study published in BMJ Global Health used mathematical models to analyze dengue virus transmission during the Indonesia trial. They explored three biases, or sources of potential error, that the trial is subject to: human movement, mosquito movement and the combined transmission dynamics between human and mosquito movement.
Dengue rates drop after release of modified mosquitoes in Colombia
28270M. Lenharo, Nature, 2023-10-27 07:52:00.
Three cities in Colombia saw a dramatic fall in the incidence of dengue in the years following the introduction of mosquitoes carrying Wolbachia, a bacterium that prevents the insect from transmitting viruses. In neighbourhoods where the Wolbachia mosquitoes were well established, dengue incidence dropped by 94–97%. The Aedes aegypti mosquitoes were released by the World Mosquito Program (WMP), a non-profit organization that has been conducting similar experiments in Australia, Brazil, Indonesia and Vietnam, among other countries. In Colombia, the modified mosquitoes were released in one of the country’s most populous regions. “That’s the largest continuous releases of Wolbachia [mosquitoes] globally so far, in terms of the population covered and the area,” says Katie Anders, an epidemiologist at the WMP and Monash University in Melbourne, Australia. Anders presented the results on 22 October at the annual meeting of the American Society of Tropical Medicine and Hygiene in Chicago, Illinois.
Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host
28215S. L. Russell, J. R. Castillo and W. T. Sullivan, PLOS Biology, 21:e3002335. 2023-10-24 14:41:16.
The alphaproteobacterium Wolbachia pipientis infects arthropod and nematode species worldwide, making it a key target for host biological control. Wolbachia-driven host reproductive manipulations, such as cytoplasmic incompatibility (CI), are credited for catapulting these intracellular bacteria to high frequencies in host populations. Positive, perhaps mutualistic, reproductive manipulations also increase infection frequencies, but are not well understood. Here, we identify molecular and cellular mechanisms by which Wolbachia influences the molecularly distinct processes of germline stem cell (GSC) self-renewal and differentiation. We demonstrate that wMel infection rescues the fertility of flies lacking the translational regulator mei-P26and is sufficient to sustain infertile homozygous mei-P26knockdown stocks indefinitely. Cytology revealed that wMel mitigates the impact of mei-P26 loss through restoring proper pMad, Bam, Sxl, and Orb expression. In Oregon R files with wild-type fertility, wMel infection elevates lifetime egg hatch rates. Exploring these phenotypes through dual-RNAseq quantification of eukaryotic and bacterial transcripts revealed that wMel infection rescues and offsets many gene expression changes induced by meiP26loss at the mRNA level. Overall, we show that wMel infection beneficially reinforces host fertility at mRNA, protein, and phenotypic levels, and these mechanisms may promote the emergence of mutualism and the breakdown of host reproductive manipulations.
How mosquito-controlling bacteria might also enhance insect fertility
28212Public Library of Science, Phys Org, 2023-10-24 13:51:56.
A new study reveals biological mechanisms by which a specific strain of bacteria in the Wolbachia genus might enhance the fertility of the insects it infects—with potentially important implications for mosquito-control strategies. Shelbi Russell of the University of California Santa Cruz, US, and colleagues reported these findings in the open access journal PLOS Biology on October 24th. Different strains of Wolbachia bacteria naturally infect a number of different animals worldwide, such as mosquitos, butterflies, and fruit flies. Wolbachia can manipulate the fertility of their hosts through a specific biological mechanism that aids the spread of Wolbachia within host populations. In recent years, people have harnessed that mechanism in strategies to deliberately infect mosquitos with a specific Wolbachia strain, reducing targeted mosquito populations and thereby potentially reducing the spread of human viruses carried by mosquitos, such as dengue or Zika.
Wolbachia enhances the survival ofDrosophila infected with fungal pathogens
28218J. Perlmutter, I., A. Atadurdyyeva, M. Schedl, E. and R. Unckless, L., bioRxiv, 2023.09.30.560320. 2023-10-11 14:49:32.
Wolbachia bacteria of arthropods are at the forefront of basic and translational research on multipartite host-symbiont-pathogen interactions. These microbes are vertically inherited from mother to offspring via the cytoplasm. They are the most widespread endosymbionts on the planet due to their infamous ability to manipulate the reproduction of their hosts to spread themselves in a population, and to provide a variety of fitness benefits to their hosts. Importantly, some strains of Wolbachia can inhibit viral pathogenesis within and between arthropod hosts. Mosquitoes carrying the wMel Wolbachia strain of Drosophila melanogaster have a greatly reduced capacity to spread viruses like dengue and Zika to humans. Therefore, Wolbachia are the basis of several global vector control initiatives. While significant research efforts have focused on viruses, relatively little attention has been given to Wolbachia-fungal interactions despite the ubiquity of fungal entomopathogens in nature. Here, we demonstrate that Wolbachia increase the longevity of their Drosophila melanogaster hosts when challenged with a spectrum of yeast and filamentous fungal pathogens. We find that this pattern can vary based on host genotype, sex, and fungal species. Further, Wolbachia correlates with higher fertility and reduced pathogen titers during initial fungal infection, indicating a significant fitness benefit. This study demonstrates Wolbachia’s role in diverse fungal pathogen interactions and determines that the phenotype is broad, but with several variables that influence both the presence and strength of the phenotype. These results enhance our knowledge of the strategies Wolbachia uses that likely contribute to such a high global symbiont prevalence.Importance Wolbachia bacteria of arthropods are at the forefront of global initiatives to fight arthropod-borne viruses. Despite great success in using the symbiont to fight viruses, little research has focused on Wolbachia-fungal interactions. Here, we find that Wolbachia of Drosophila melanogaster, the same strain widely used in antiviral initiatives, can also increase the longevity of flies systemically infected with a panel of yeast and filamentous fungal pathogens. The symbiont also partially increases host fertility and reduces fungal titers during early infection, indicating a significant fitness benefit. This represents a major step forward in Wolbachia research since its pathogen blocking abilities can now be extended to a broad diversity of another major branch of microbial life. This discovery may inform basic research on pathogen blocking and has potential translational applications in areas including biocontrol in agriculture.Competing Interest StatementThe authors have declared no competing interest.
Wolbachia interferes with Zika virus replication by hijacking cholesterol metabolism in mosquito cells
28094B. Edwards, E. A.-O. X. Ghedin and D. A.-O. Voronin, Microbiology Spectrum, 2023-10-09 07:37:16.
Zika virus is a member of the arbovirus Flaviviridae family transmitted by Aedes mosquitos and it is associated with microcephaly in infants born to infected mothers. Wolbachia is an intracellular gram-negative alpha-proteobacteria that infects many species of arthropods, including mosquitos. The presence of Wolbachia in mosquitos has been shown to control the vector population and suppress arbovirus transmission. One mechanism of Wolbachia-mediated interference with virus replication is competition over host resources between Wolbachia and the virus. We hypothesize that cholesterol metabolism is involved in Wolbachia-mediated virus suppression due to its important role in Zika virus replication. In this study, we determined that Wolbachia impacted virus replication by altering cholesterol biosynthesis in Aedes albopictus C6/36 cells, diverting resources from the host cell mevalonate (MVA) pathway to fulfill the needs of the bacteria. This resulted in a decrease of total cholesterol, increased Wolbachia loads, and decreased viral titers. Inhibition of the MVA pathway using fluvastatin decreased total cholesterol and viral titers, mimicking the effects of Wolbachia on the virus in Wolbachia-free cells. We also found that Wolbachia-infected cells had depleted lipid droplets, the main component of which is cholesterol esters. We confirmed that cholesterol esterases were upregulated in response to virus infection in C6/36 cells. Functional analysis showed that alteration of cholesterol metabolism simulated Wolbachia-mediated inhibition of virus infection in C6/36 cells. Our study provides a mechanism behind Wolbachia-induced interference of arbovirus replication and could help advance strategies to control arbovirus pathogens in insect vectors and human infections. IMPORTANCE Arthropod-borne viruses are emerging pathogens that are spread widely by mosquitos. Zika virus is an arbovirus that can infect humans and be transmitted from an infected mother to the fetus, potentially leading to microcephaly in infants. One promising strategy to prevent disease caused by arboviruses is to target the insect vector population. Recent field studies have shown that mosquito populations infected with Wolbachia bacteria suppress arbovirus replication and transmission. Here, we describe how intracellular bacteria redirect resources within their host cells and suppress Zika virus replication at the cellular level. Understanding the mechanism behind Wolbachia-induced interference of arbovirus replication could help advance strategies to control arbovirus pathogens in insect vectors and human populations. FAU - Edwards, Brent
Millions of Mosquitoes Will Rain Down on Hawaii to Save an Iconic Bird
28010S. Wild, Scientific American, 2023-10-06 06:53:13.
Millions of mosquitoes dropped from helicopters could be the greatest hope for Hawaii’s iconic honeycreepers. At least four species of the brightly colored birds could go extinct within the year if no action is taken to save them. “We’re seriously in a race against time at the moment,” says Hanna Mounce, program manager of the Maui Forest Bird Recovery Project. These small birds evolved on the islands over the course of millions of years and are uniquely adapted to their niche habitat, where they are crucial pollinators for many of Hawaii’s flora. For the people of Hawaii, the honeycreepers are also woven into the cultural fabric, featuring prominently in many legends and providing feathers for traditional garments. More than 50 species of honeycreepers once flitted across the archipelago, but because of introduced predators, habitat destruction and disease, that number has dwindled to only 17. Invasive Culex quinquefasciatus mosquitoes—possibly introduced via water barrels on European ships in the early 19th century—pose a particular threat because they spread the deadly avian malaria parasite.IIT works like this: C. quinquefasciatus mosquitoes, as well as many other arthropods, naturally contain Wolbachia bacteria in their gut. In order to produce offspring together, mating mosquitoes must be infected with the same strain of the bacteria. Birds, Not Mosquitoes’ plan involves releasing male mosquitoes bred by Verily Life Sciences—the life sciences research arm of Alphabet, which also owns Google. These mosquitos will host a different Wolbachia strain than those on Maui. The idea is that the existing female mosquitoes will mate with the male newcomers, but because of their incompatible Wolbachia bacteria, they will not produce viable offspring. If all goes according to plan, the overall mosquito population will plummet.
The double-edged sword effect of expanding Wolbachia deployment in dengue endemic settings
28137M. G. Pavan, G. A. Garcia, M. R. David and R. Maciel-de-Freitas, The Lancet Regional Health - Americas, 27:100610. 2023-10-02 10:16:37.
We can use Brazil as a showcase to foresee and avoid a double-edged sword effect associated with Wolbachia releases. Insecticide resistance of native Ae. aegypti populations is spread worldwide (http://aedes.irmapper.com), and positive results should boost Wolbachia deployment in other dengue endemic settings around the world. Aedes aegypti populations are heterogeneous and nationwide releases of a Wolbachia strain whose genetic backcross belong to a specific locality would produce an unsought homogenization of vector populations. Aedes aegypti homogenisation at large geographic scales could impose additional undesirable consequences in the long-term by promoting genetic hitchhiking of traits such as higher vector competence, lower susceptibility to repellents and insecticides, or more avid host-seeking and biting behaviour. Available data has shown that ensuring adherence to local characteristics, specially a matching genetic between native and released mosquitoes, is critical to enhance the likelihood of achieving a faster introgression in the field, realizing cost and time savings over the globe. Probably there are a myriad of yet undiscovered traits beyond insecticide resistance that may influence vector local adaptation and would affect the success of released strains. Therefore, neglecting the genetic diversity in favour of centralising the rearing of mosquitoes with Wolbachia for nationwide releases could represent a drawback for future releases. Long-term studies regarding the consequences of releasing mosquitoes with homogenous genotypes in diverse ecological and epidemiological scenarios remain a critical research priority, essential for informed decision-making and sustainable management of mosquito-borne diseases.
Wolbachia-mediated resistance to Zika virus infection in Aedes aegypti is dominated by diverse transcriptional regulation and weak evolutionary pressures
27974E. C. Boehm, A. S. Jaeger, H. J. Ries, D. Castañeda, A. M. Weiler, C. C. Valencia, J. Weger-Lucarelli, G. D. Ebel, S. L. O’Connor, T. C. Friedrich, M. Zamanian and M. T. Aliota, PLOS Neglected Tropical Diseases, 17:e0011674. 2023-10-02 07:38:35.
A promising candidate for arbovirus control and prevention relies on replacing arbovirus-susceptible Aedes aegypti populations with mosquitoes that have been colonized by the intracellular bacterium Wolbachia and thus have a reduced capacity to transmit arboviruses. This reduced capacity to transmit arboviruses is mediated through a phenomenon referred to as pathogen blocking. Pathogen blocking has primarily been proposed as a tool to control dengue virus (DENV) transmission, however it works against a range of viruses, including Zika virus (ZIKV). Despite years of research, the molecular mechanisms underlying pathogen blocking still need to be better understood. Here, we used RNA-seq to characterize mosquito gene transcription dynamics in Ae. aegypti infected with the wMel strain of Wolbachia that are being released by the World Mosquito Program in Medellín, Colombia. Comparative analyses using ZIKV-infected, uninfected tissues, and mosquitoes without Wolbachia revealed that the influence of wMel on mosquito gene transcription is multifactorial. Importantly, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to pathogen blocking. Therefore, to understand the influence of Wolbachia on within-host ZIKV evolution, we characterized the genetic diversity of molecularly barcoded ZIKV virus populations replicating in Wolbachia-infected mosquitoes and found that within-host ZIKV evolution was subject to weak purifying selection and, unexpectedly, loose anatomical bottlenecks in the presence and absence of Wolbachia. Together, these findings suggest that there is no clear transcriptional profile associated with Wolbachia-mediated ZIKV restriction, and that there is no evidence for ZIKV escape from this restriction in our system.
Unleashing a New Weapon on the Mosquito: A Mosquito
27987S. Nolen and E. Lutz, New York Times, 2023-09-29 08:05:43.
Five decades ago, entomologists confronting the many kinds of suffering that mosquitoes inflict on humans began to consider a new idea: What if, instead of killing the mosquitoes (a losing proposition in most places), you could disarm them? Even if you couldn’t keep them from biting people, what if you could block them from passing on disease? What if, in fact, you could use one infectious microbe to stop another? These scientists began to consider a parasitic bacteria called Wolbachia, which lives quietly in all kinds of insect species. A female mosquito with Wolbachia passes it on in her eggs to all of her offspring, who eventually pass it on to the next generation. But Wolbachia isn’t naturally found in the mosquito species that cause humans the most problems — the Aedes aegypti, the virus carrier, and the Anopheles subspecies, which carry malaria. If it were, it might eventually render those species essentially harmless. So how do you infect a mosquito with Wolbachia?
Wolbachia Induces Structural Defects Harmful to Drosophila simulans Riverside Spermiogenesis.
28142M. G. Riparbelli, A. Pratelli and G. Callaini, Cells, 12. 2023-09-21 10:31:00.
The relationship between cytoplasmic incompatibility and the obligate intracellular alphaproteobacteria Wolbachia has for a long time been reported. Although the molecular mechanisms responsible for this reproductive alteration are beginning to be understood, the effects of Wolbachia on germ cell structure and dynamics have not yet been fully investigated. We report here that the presence of Wolbachia in infected cysts of elongating spermatids is associated with major structural defects that become more evident in mature sperm. We find mitochondrial defects, an improper axoneme structure, reduced sperm numbers, and individualization failures. The large heterogeneous variety of the ultrastructural defects found in elongating spermatids and mature sperm provide the first cytological evidence for the reduced fertility associated with Wolbachia infection in Drosophila simulans males. The observed abnormalities could be the result of the mechanical stress induced by the high bacteria numbers during the process of spermatid elongation, rather than the result of the released factors affecting the proper morphogenesis of the germ cells. Moreover, high Wolbachia densities in male germ cells may not be appropriate for causing cytoplasmic incompatibility as the bacteria are harmful for spermatid differentiation, leading to abnormal sperm that is unlikely to be functional.
Using Wolbachia to control rice planthopper populations: progress and challenges
27976Y. Guo, J. Shao, Y. Wu and Y. Li, Frontiers in Microbiology, 14. 2023-09-14 07:43:50.
Wolbachia have been developed as a tool for protecting humans from mosquito populations and mosquito-borne diseases. The success of using Wolbachia relies on the facts that Wolbachia are maternally transmitted and that Wolbachia-induced cytoplasmic incompatibility provides a selective advantage to infected over uninfected females, ensuring that Wolbachia rapidly spread through the target pest population. Most transinfected Wolbachia exhibit a strong antiviral response in novel hosts, thus making it an extremely efficient technique. Although Wolbachia has only been used to control mosquitoes so far, great progress has been made in developing Wolbachia-based approaches to protect plants from rice pests and their associated diseases. Here, we synthesize the current knowledge about the important phenotypic effects of Wolbachia used to control mosquito populations and the literature on the interactions between Wolbachia and rice pest planthoppers. Our aim is to link findings from Wolbachia-mediated mosquito control programs to possible applications in planthoppers.
Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia
27831Ogunlade, S. T. Adekunle, A. I. Meehan, M. T. McBryde, E. S., Scientific Reports, 13:14932. 2023-09-11 08:51:39.
From October 2014 to February 2019, local authorities in Townsville, North Queensland, Australia continually introduced Wolbachia-infected mosquitoes to control seasonal outbreaks of dengue infection. In this study, we develop a mathematical modelling framework to estimate the effectiveness of this intervention as well as the relative dengue transmission rates of Wolbachia-infected and wild-type mosquitoes. We find that the transmission rate of Wolbachia-infected mosquitoes is reduced approximately by a factor of 20 relative to the uninfected wild-type population. In addition, the Townsville Wolbachia release program led to a 65% reduction in predicted dengue incidence during the release period and over 95% reduction in the 24 months that followed. Finally, to investigate the potential impact of other Wolbachia release programs, we use our estimates of relative transmissibility to calculate the relationship between the reproductive number of dengue and the proportion of Wolbachia-infected mosquitoes in the vector population.
Molecular Evidence of Wolbachia Species in Wild-Caught Aedes albopictus and Aedes aegypti Mosquitoes in Four States of Northeast India
27843Vinayagam, S. Nirmolia, T. Chetry, S. Kumar, N. P. Saini, P. Bhattacharyya, D. R. Bhowmick, I. P. Sattu, K. Patgiri, S. J., Journal of Tropical Medicine, 2023-09-05 09:37:52.
Wolbachia, a Gram-negative intracellular bacterium, naturally infects many arthropods, including mosquito vectors responsible for the spread of arboviral diseases such as Zika, chikungunya, and dengue fever. Certain Wolbachia strains are involved in inhibiting arbovirus replication in mosquitoes, and this phenomenon is currently being studied to combat disease vectors. A study was conducted in four states in north-eastern India to investigate the presence of natural Wolbachia infection in wild-caught Aedes albopictus and Aedes aegypti mosquitoes, the established vectors of dengue. The detection of a Wolbachia infection was confirmed by nested PCR and sequencing in the two mosquito species Ae. aegypti and Ae. albopictus. Positivity rates observed in Ae. aegypti and Ae. albopictus pools were 38% (44 of 115) and 85% (41 of 48), respectively, and the difference was significant (chi-square = 28.3174, p = 0.00000010). Sequencing revealed that all detected Wolbachia strains belonged to supergroup B. Although Wolbachia infection in Ae. aegypti has been previously reported from India, no such reports are available from north-eastern India. Data on naturally occurring Wolbachia strains are essential for selecting the optimal strain for the development of Wolbachia-based control measures. This information will be helpful for the future application of Wolbachia-based vector control measures in this part of the country.
Jamestown Canyon virus is transmissible by Aedes aegypti and is only moderately blocked by Wolbachia co-infection
27755M. J. Lau, H. L. C. Dutra, M. J. Jones, B. P. McNulty, A. M. Diaz, F. Ware-Gilmore and E. A. McGraw, PLOS Neglected Tropical Diseases, 17. 2023-09-05 07:50:16.
Jamestown Canyon virus (JCV), a negative-sense arbovirus, is increasingly common in the upper Midwest of the USA. Transmitted by a range of mosquito genera, JCV's primary amplifying host is white-tailed deer. Aedes aegypti is responsible for transmitting various positive-sense viruses globally including dengue (DENV), Zika, chikungunya, and Yellow Fever. Ae. aegypti's distribution, once confined to the tropics, is expanding, in part due to climate change. Wolbachia, an insect endosymbiont, limits the replication of co-infecting viruses inside insects. The release and spread of the symbiont into Ae. aegypti populations have been effective in reducing transmission of DENV to humans, although the mechanism of Wolbachia-mediated viral blocking is still poorly understood. Here we explored JCV infection potential in Ae. aegypti, the nature of the vector's immune response, and interactions with Wolbachia infection. We show that Ae. aegypti is highly competent for JCV, which grows to high loads and rapidly reaches the saliva after an infectious blood meal. The mosquito immune system responds with strong induction of RNAi and JAK/STAT. Neither the direct effect of viral infection nor the energetic investment in immunity appears to affect mosquito longevity. Wolbachia infection blocked JCV only in the early stages of infection. Wolbachia-induced immunity was small compared to that of JCV, suggesting innate immune priming does not likely explain blocking. We propose two models to explain why Wolbachia's blocking of negative-sense viruses like JCV may be less than that of positive-sense viruses, relating to the slowdown of host protein synthesis and the triggering of interferon-like factors like Vago. In conclusion, we highlight the risk for increased human disease with the predicted future overlap of Ae. aegypti and JCV ranges. We suggest that with moderate Wolbachia-mediated blocking and distinct biology, negative-sense viruses represent a fruitful comparator model to other viruses for understanding blocking mechanisms in mosquitoes.
Does ignoring transmission dynamics lead to underestimation of the impact of interventions against mosquito-borne disease?
27695S. Cavany, J. Huber, H. , A. Wieler, Q. M. Tran, M. Alkuzweny, M. Elliott, G. España, S. Moore, M. and T. A. Perkins, BMJ Global Health, 8:e012169. 2023-08-31 09:07:49.
New vector-control technologies to fight mosquito-borne diseases are urgently needed, the adoption of which depends on efficacy estimates from large-scale cluster-randomised trials (CRTs). The release of Wolbachia-infected mosquitoes is one promising strategy to curb dengue virus (DENV) transmission, and a recent CRT reported impressive reductions in dengue incidence following the release of these mosquitoes. Such trials can be affected by multiple sources of bias, however. We used mathematical models of DENV transmission during a CRT of Wolbachia-infected mosquitoes to explore three such biases: human movement, mosquito movement and coupled transmission dynamics between trial arms. We show that failure to account for each of these biases would lead to underestimated efficacy, and that the majority of this underestimation is due to a heretofore unrecognised bias caused by transmission coupling. Taken together, our findings suggest that Wolbachia-infected mosquitoes could be even more promising than the recent CRT suggested. By emphasising the importance of accounting for transmission coupling between arms, which requires a mathematical model, we highlight the key role that models can play in interpreting and extrapolating the results from trials of vector control interventions.Data are available in a public, open access repository. All code and other files to reproduce our results is available at: https://github.com/scavany/awed_trial_modeling/
Wolbachia wMel strain-mediated effects on dengue virus vertical transmission from Aedes aegypti to their offspring
27693K. Duong Thi Hue, D. da Silva Goncalves, V. Tran Thuy, L. Thi Vo, D. Le Thi, N. Vu Tuyet, G. Nguyen Thi, T. Huynh Thi Xuan, N. Nguyen Minh, P. Nguyen Thanh, S. Yacoub and C. P. Simmons, Parasites and Vectors, 16:308. 2023-08-31 08:53:50.
Background Dengue virus serotypes (DENV-1 to -4) can be transmitted vertically in Aedes aegpti mosquitoes. Whether infection with the wMel strain of the endosymbiont Wolbachia can reduce the incidence of vertical transmission of DENV from infected females to their offspring is not well understood. Methods A laboratory colony of Vietnamese Ae. aegypti, both with and without wMel infection, were infected with DENV-1 by intrathoracic injection (IT) to estimate the rate of vertical transmission (VT) of the virus. VT in the DENV-infected mosquitoes was calculated via the infection rate estimation from mosquito pool data using maximum likelihood estimation (MLE). Results In 6047 F1 Vietnamese wild-type Ae. aegypti, the MLE of DENV-1 infection was 1.49 per 1000 mosquitoes (95% confidence interval [CI] 0.73–2.74). In 5500 wMel-infected Ae. aegypti, the MLE infection rate was 0 (95% CI 0–0.69). The VT rates between mosquito lines showed a statistically significant difference. Conclusions The results reinforce the view that VT is a rare event in wild-type mosquitoes and that infection with wMel is effective in reducing VT.
Wolbachia has subtle effects on thermal preference in highly inbred Drosophila melanogaster which vary with life stage and environmental conditions
27676A. Strunov, C. Schoenherr and M. Kapun, Scientific Reports, 13:13792. 2023-08-23 07:09:52.
Temperature fluctuations are challenging for ectotherms which are not able to regulate body temperature by physiological means and thus have to adjust their thermal environment via behavior. However, little is yet known about whether microbial symbionts influence thermal preference (Tp) in ectotherms by modulating their physiology. Several recent studies have demonstrated substantial effects of Wolbachia infections on host Tp in different Drosophila species. These data indicate that the direction and strength of thermal preference variation is strongly dependent on host and symbiont genotypes and highly variable among studies. By employing highly controlled experiments, we investigated the impact of several environmental factors including humidity, food quality, light exposure, and experimental setup that may influence Tp measurements in adult Drosophila melanogaster flies. Additionally, we assessed the effects of Wolbachia infection on Tp of Drosophila at different developmental stages, which has not been done before. We find only subtle effects of Wolbachia on host Tp which are strongly affected by experimental variation in adult, but not during juvenile life stages. Our in-depth analyses show that environmental variation has a substantial influence on Tp which demonstrates the necessity of careful experimental design and cautious interpretations of Tp measurements together with a thorough description of the methods and equipment used to conduct behavioral studies.
The impact of predators of mosquito larvae on Wolbachia spreading dynamics
27651Z. Zhu, Y. Hui and L. Hu, Journal of Biological Dynamics, 17:2249024. 2023-08-21 07:05:13.
Dengue fever creates more than 390 million cases worldwide yearly. The most effective way to deal with this mosquito-borne disease is to control the vectors. In this work we consider two weapons, the endosymbiotic bacteria Wolbachia and predators of mosquito larvae, for combating the disease. As Wolbachia-infected mosquitoes are less able to transmit dengue virus, releasing infected mosquitoes to invade wild mosquito populations helps to reduce dengue transmission. Besides this measure, the introduction of predators of mosquito larvae can control mosquito population. To evaluate the impact of the predators on Wolbachia spreading dynamics, we develop a stage-structured five-dimensional model, which links the predator-prey dynamics with the Wolbachia spreading. By comparatively analysing the dynamics of the models without and with predators, we observe that the introduction of the predators augments the number of coexistence equilibria and impedes Wolbachia spreading. Some numerical simulations are presented to support and expand our theoretical results.
wMel Wolbachia alters female post-mating behaviors and physiology in the dengue vector mosquito Aedes aegypti
27649J. Osorio, S. Villa-Arias, C. Camargo, L. F. Ramírez-Sánchez, L. M. Barrientos, C. Bedoya, G. Rúa-Uribe, S. Dorus, C. Alfonso-Parra and F. W. Avila, Communications Biology, 6:865. 2023-08-21 06:53:59.
Globally invasive Aedes aegypti disseminate numerous arboviruses that impact human health. One promising method to control Ae. aegypti populations is transinfection with Wolbachia pipientis, which naturally infects ~40–52% of insects but not Ae. aegypti. Transinfection of Ae. aegypti with the wMel Wolbachia strain induces cytoplasmic incompatibility (CI), allows infected individuals to invade native populations, and inhibits transmission of medically relevant arboviruses by females. Female insects undergo post-mating physiological and behavioral changes—referred to as the female post-mating response (PMR)—required for optimal fertility. PMRs are typically elicited by male seminal fluid proteins (SFPs) transferred with sperm during mating but can be modified by other factors, including microbiome composition. Wolbachia has modest effects on Ae. aegypti fertility, but its influence on other PMRs is unknown. Here, we show that Wolbachia influences female fecundity, fertility, and re-mating incidence and significantly extends the longevity of virgin females. Using proteomic methods to examine the seminal proteome of infected males, we found that Wolbachia moderately affects SFP composition. However, we identified 125 paternally transferred Wolbachia proteins, but the CI factor proteins (Cifs) were not among them. Our findings indicate that Wolbachia infection of Ae. aegypti alters female PMRs, potentially influencing control programs that utilize Wolbachia-infected individuals.
Wolbachia infection at least partially rescues the fertility and ovary defects of several new Drosophila melanogaster bag of marbles protein-coding mutants
27701W. Miwa and F. A. Charles, bioRxiv, 2023.03.20.532813. 2023-08-16 09:19:09.
The D. melanogaster protein coding gene bag of marbles (bam) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene, Sex lethal, bam genetically interacts with the endosymbiont Wolbachia, as Wolbachia rescues the reduced fertility of a bam hypomorphic mutant. Here, we explored the specificity of the bam-Wolbachia interaction by generating 22 new bam mutants, with ten mutants displaying fertility defects. Nine of these mutants trend towards rescue by the wMel Wolbachia variant, with eight statistically significant at the fertility and/or cytological level. In some cases, fertility was increased a striking 20-fold. There is no specificity between the rescue and the known binding regions of bam, suggesting wMel does not interact with one singular bam partner to rescue the reproductive phenotype. We further tested if wMel interacts with bam in a non-specific way, by increasing bam transcript levels or acting upstream in germline stem cells. A fertility assessment of a bam RNAi knockdown mutant reveals that wMel rescue is specific to functionally mutant bam alleles and we find no obvious evidence of wMel interaction with germline stem cells in bam mutants.Author Summary Reproduction in the Drosophila melanogaster fruit fly is dependent on the bag of marbles (bam) gene, which acts early in the process of generating eggs and sperm. Mutations to this gene negatively impact the fertility of the fly, causing it to be sterile or have fewer progeny. Interestingly, we find that the bacteria Wolbachia, which resides within reproductive cells across a wide range of insects, partially restores the fertility and ovary phenotype of several bam mutants of which the resultant Bam protein is altered from wildtype. The protein function of Bam is further suggested to be important by the lack of rescue for a fly that has a fertility defect due to low expression of a non-mutated bam gene. Previous work makes similar conclusions about Wolbachia with another reproductive gene, Sex lethal (Sxl), highlighting the potential for rescue of fertility mutants to occur in a similar way across different genes. An understanding of the ways in which Wolbachia can affect host reproduction provides us with context with which to frame Wolbachia’s impact on host genes, such as bam and Sxl, and consider the evolutionary implications of Wolbachia’s infection in D. melanogaster fruit flies.Competing Interest StatementThe authors have declared no competing interest.
Modeling shows emerging mosquito control approach might be largely resistant to warming temperatures
27595B. Yirka, Phys Org, 2023-08-07 06:48:13.
A team of epidemiologists and engineers at the University of California, working with a colleague from QIMR Berghofer Medical Research Institute, in Australia, has found via modeling that the use of the Wolbachia approach to slowing the spread of mosquito-borne diseases (MBDs) is likely to survive climate change—at least in the near term. In their study, reported in the journal Nature Climate Change, the group used population dynamic models using data on mosquitos and Wolbachia bacteria along with temperature increases due to climate change. Eric Caragata, with the University of Florida, has published a News & Views piece in the same journal issue, outlining the work done by the team on this new effort.
Scientists are releasing disease-resistant mosquitoes. But heat waves could kill them.
27586C. Harvey, Politico, 2023-08-04 08:21:30.
A new study, published Thursday in the journal Nature Climate Change, suggests that the disease-quashing bugs will likely survive for at least the next couple of decades. Their fate is less certain further into the future. The study focuses on a special insect-borne bacterium called Wolbachia, which has natural virus-blocking properties and is carried in different insect populations, including some mosquito species. It’s not typically found in Aedes aegypti, or the “yellow fever mosquito,” one of the most significant disease-carrying species on the planet. But scientists have figured out ways to introduce the bacteria into Aedes aegypti populations — and potentially slow the transmission of diseases including yellow fever and dengue fever and the Zika and chikungunya viruses.
wMel replacement of dengue-competent mosquitoes is robust to near-term change
27584V. N. Vásquez, L. M. Kueppers, G. Rašić and J. M. Marshall, Nature Climate Change, 13:848-855. 2023-08-01 08:16:33.
Rising temperatures are impacting the range and prevalence of mosquito-borne diseases. A promising biocontrol technology replaces wild mosquitoes with those carrying the virus-blocking Wolbachia bacterium. Because the most widely used strain, wMel, is adversely affected by heat stress, we examined how global warming may influence wMel-based replacement. We simulated interventions in two locations with successful field trials using Coupled Model Intercomparison Project Phase 5 climate projections and historical temperature records, integrating empirical data on wMel’s thermal sensitivity into a model of Aedes aegypti population dynamics to evaluate introgression and persistence over one year. We show that in Cairns, Australia, climatic futures necessitate operational adaptations for heatwaves exceeding two weeks. In Nha Trang, Vietnam, projected heatwaves of three weeks and longer eliminate wMel under the most stringent assumptions of that symbiont’s thermal limits. We conclude that this technology is generally robust to near-term (2030s) climate change. Accelerated warming may challenge this in the 2050s and beyond.
Susceptibility of Wolbachia mosquito control to temperature shifts
27579E. P. Caragata, Nature Climate Change, 13:767-768. 2023-08-01 08:10:19.
Vásquez and colleagues consider the potential impacts of increasing and variable temperatures on Wolbachia-based population-replacement interventions. Previous laboratory experiments have highlighted the temperature-sensitive nature of Wolbachia, with high average daily temperatures and prolonged heatwaves potentially decreasing Wolbachia titre, leading to weakening or loss of maternal transmission, cytoplasmic incompatibility and virus blocking . In nature, this could potentially hinder or thwart interventions. Vásquez and colleagues use Coupled Model Intercomparison Project Phase 5 climate projections to model the efficacy of population-replacement interventions utilizing the wMel Wolbachia strain in Ae. aegypti in Cairns, Australia, and in Nha Trang, Vietnam, two current intervention sites. Their mechanistic models compare population-replacement efficiency under current temperature regimes, and those projected for the 2030s (2024–2039) and 2050s (2044–2059). These models also incorporate loss of wMel infection at an average daily temperature threshold of 35 °C (based on laboratory data ), or more stringently, at 33 °C or 31.5 °C.
Lab-grown special mosquitoes can be the secret weapon to fight dengue
26965M. Jain, MONGABAY, 2023-07-20 10:11:50.
The World Mosquito Program infects the Aedes aegypti, which carries the dengue virus, with a bacteria called Wolbachia, which reduces the transmission of dengue. Dengue infections are rapidly increasing because of factors like urbanisation and climate change. The World Health Organization estimates approximately 390 million dengue infections annually, with 3.9 billion people at risk. In India, the Indian Council of Medical Research’s Vector Control Research Centre (VCRC) has been studying this method since 2016 to assess if it works against dengue, which has been increasing in the country.
Modeling the Impact of Migration on Mosquito Population Suppression
27422M. Huang and J. Yu, Qualitative Theory of Dynamical Systems, 22:134. 2023-07-17 08:45:23.
The Wolbachia-induced incompatible insect technique is a promising strategy for controlling wild mosquito populations. However, recent experimental studies have shown that mosquito migration into target areas dilutes the strategy’s effectiveness. In this work, we formulate a delay differential equation model to assess the impact of migration on mosquito population suppression. We identify that mosquito migration into an idealized target area makes it impossible to eliminate the target population completely. Our analysis identifies a lower bound of the suppression rate $$gamma ^*$$for a given migration number, which reveals the possible maximum reduction of wild population size in the peak season. For a given suppression rate target $$gamma _0>gamma ^*$$, we identify the permitted maximum migration number $$D(gamma _0)$$, above which is impossible to reduce the field mosquito density up to $$(1-gamma _0)times 100%$$in peak season. To reduce more than $$95%$$of Aedes albopictus population during its peak season in Guangzhou within six weeks, the required minimum release number of Wolbachia-infected males climbs steeply as the migration number increases to D(0.05).
26619
N. Wybouw, E. Van Reempts, J. Zarka, F. Zélé and D. Bonte, Heredity, 2023-07-13 08:18:54.
Maternally transmitted symbionts such as Wolbachia can alter sex allocation in haplodiploid arthropods. By biasing population sex ratios towards females, these changes in sex allocation may facilitate the spread of symbionts. In contrast to symbiont-induced cytoplasmic incompatibility (CI), the mechanisms that underpin sex allocation distortion remain poorly understood. Using a nuclear genotype reference panel of the haplodiploid mite Tetranychus urticae and a single Wolbachia variant that is able to simultaneously induce sex allocation distortion and CI, we unraveled the mechanistic basis of Wolbachia-mediated sex allocation distortion. Host genotype was an important determinant for the strength of sex allocation distortion. We further show that sex allocation distortion by Wolbachia in haplodiploid mites is driven by increasing egg size, hereby promoting egg fertilization. This change in reproductive physiology was also coupled to increased male and female adult size. Our results echo previous work on Cardinium symbionts, suggesting that sex allocation distortion by regulating host investment in egg size is a common strategy among symbionts that infect haplodiploids. To better understand the relevance that sex allocation distortion may have for the spread of Wolbachia in natural haplodiploid populations, we parametrized a model based on generated phenotypic data. Our simulations show that empirically derived levels of sex allocation distortion can be sufficient to remove invasion thresholds, allowing CI to drive the spread of Wolbachia independently of the initial infection frequency. Our findings help elucidate the mechanisms that underlie the widespread occurrence of symbionts in haplodiploid arthropods and the evolution of sex allocation.
The cellular lives of Wolbachia
26608J. Porter and W. Sullivan, Nature Reviews Microbiology, 2023-07-10 13:14:07.
Wolbachia are successful Gram-negative bacterial endosymbionts, globally infecting a large fraction of arthropod species and filarial nematodes. Efficient vertical transmission, the capacity for horizontal transmission, manipulation of host reproduction and enhancement of host fitness can promote the spread both within and between species. Wolbachia are abundant and can occupy extraordinary diverse and evolutionary distant host species, suggesting that they have evolved to engage and manipulate highly conserved core cellular processes. Here, we review recent studies identifying Wolbachia–host interactions at the molecular and cellular levels. We explore how Wolbachia interact with a wide array of host cytoplasmic and nuclear components in order to thrive in a diversity of cell types and cellular environments. This endosymbiont has also evolved the ability to precisely target and manipulate specific phases of the host cell cycle. The remarkable diversity of cellular interactions distinguishes Wolbachia from other endosymbionts and is largely responsible for facilitating its global propagation through host populations. Finally, we describe how insights into Wolbachia–host cellular interactions have led to promising applications in controlling insect-borne and filarial nematode-based diseases.
Threshold dynamics of a stochastic mathematical model for Wolbachia infections
26546J. Yang, Z. Chen, Y. Tan, Z. Liu and R. A. Cheke, Journal of Biological Dynamics, 17:2231967. 2023-07-07 08:51:13.
A stochastic mathematical model is proposed to study how environmental heterogeneity and the augmentation of mosquitoes with Wolbachia bacteria affect the outcomes of dengue disease. The existence and uniqueness of the positive solutions of the system are studied. Then the V-geometrically ergodicity and stochastic ultimate boundedness are investigated. Further, threshold conditions for successful population replacement are derived and the existence of a unique ergodic steady-state distribution of the system is explored. The results show that the ratio of infected to uninfected mosquitoes has a great influence on population replacement. Moreover, environmental noise plays a significant role in control of dengue fever.
Wolbachia -mediated resistance to Zika virus infection in Aedes aegypti is dominated by diverse transcriptional regulation and weak evolutionary pressures
26604E. C. Boehm, A. S. Jaeger, H. J. Ries, D. Castañeda, A. M. Weiler, C. C. Valencia, J. Weger-Lucarelli, G. D. Ebel, S. L. O'Connor, T. C. Friedrich, M. Zamanian and M. T. Aliota, bioRxiv, 2023-06-26 13:09:35.
A promising candidate for arbovirus control and prevention relies on replacing arbovirus-susceptible Aedes aegypti populations with mosquitoes that have been colonized by the intracellular bacterium Wolbachia and thus have a reduced capacity to transmit arboviruses. This reduced capacity to transmit arboviruses is mediated through a phenomenon referred to as pathogen blocking. Pathogen blocking has primarily been proposed as a tool to control dengue virus (DENV) transmission, however it works against a range of viruses, including Zika virus (ZIKV). Despite years of research, the molecular mechanisms underlying pathogen blocking still need to be better understood. Here, we used RNA-seq to characterize mosquito gene transcription dynamics in Ae. aegypti infected with the w Mel strain of Wolbachia that are being released by the World Mosquito Program in Medellín, Colombia. Comparative analyses using ZIKV-infected, uninfected tissues, and mosquitoes without Wolbachia revealed that the influence of w Mel on mosquito gene transcription is multifactorial. Importantly, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to pathogen blocking. Therefore, to understand the influence of Wolbachia on within-host ZIKV evolution, we characterized the genetic diversity of molecularly barcoded ZIKV virus populations replicating in Wolbachia -infected mosquitoes and found that within-host ZIKV evolution was subject to weak purifying selection and, unexpectedly, loose anatomical bottlenecks in the presence and absence of Wolbachia . Together, these findings suggest that there is no clear transcriptional profile associated with Wolbachia -mediated ZIKV restriction, and that there is no evidence for ZIKV escape from this restriction in our system. AUTHOR SUMMARY: When Wolbachia bacteria infect Aedes aegypti mosquitoes, they dramatically reduce the mosquitoes' susceptibility to infection with a range of arthropod-borne viruses, including Zika virus (ZIKV). Although this pathogen-blocking effect has been widely recognized, its mechanisms remain unclear. Furthermore, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to Wolbachia -mediated blocking. Here, we use host transcriptomics and viral genome sequencing to examine the mechanisms of ZIKV pathogen blocking by Wolbachia and viral evolutionary dynamics in Ae. aegypti mosquitoes. We find complex transcriptome patterns that do not suggest a single clear mechanism for pathogen blocking. We also find no evidence that Wolbachia exerts detectable selective pressures on ZIKV in coinfected mosquitoes. Together our data suggest that it may be difficult for ZIKV to evolve Wolbachia resistance, perhaps due to the complexity of the pathogen blockade mechanism.
Draft environmental assessment released for using modified mosquitoes to save native birds on Kauaʻi
26244Anonymous, Big Island NOW, 2023-06-23 07:24:12.
Today, the draft environmental assessment was made public for the use of Wolbachia-based incompatible male mosquitoes on Kauaʻi to stop the spread of avian malaria that is decimating native forest bird populations. The public has 31 days — from June 23 until July 24 — to comment on the draft, which was released by the U.S. Fish and Wildlife Service and the State of Hawaiʻi Division of Forestry and Wildlife. Hawaiʻi’s forest birds are facing an extinction crisis, with avian malaria a major factor. It is transmitted by non-native mosquitoes and just a single bite from an infected mosquito can be deadly. Of Kauaʻi’s 16 native honeycreepers, 10 have gone extinct and three are listed under the Endangered Species Act as threatened or endangered.
Draft environmental assessment for use of Wolbachia-based incompatible insect technique for the suppression of nonnative southern house mosquito populations on Kauaʻi
26247Hawai'i Department of Land and Natural Resources, Hawai'i Department of Land and Natural Resources, 2023-06-16 07:31:10.
The State of Hawai'i Department of Land and Natural Resources hereby transmits the Draft Environmental Assessment and Anticipated Finding of No Significant Impact (DEAEnvironmental Assessment for use of Wolbachia-based Incompatible Insect Technique for the suppression of nonnative southern house mosquito populations o Kaua'i to be published in the next available edition of The Environmental Notice.
Effects of radiation on the fitness, sterility and arbovirus susceptibility of a Wolbachia-free Aedes albopictus strain for use in the Sterile Insect Technique
25867D. J. Zhang, S. Yan, H. Yamada, Y. Wu, G. Wang, Q. D. Feng, D. Paerhande, H. Maiga, J. Bouyer, J. Qian, Z. D. Wu and X. Y. Zheng, Pest Management Science, 2023-06-15 08:49:29.
BACKGROUND: The sterile insect technique (SIT) is a green and species-specific insect pest control technique that suppresses target populations by releasing factory-reared, radio-sterilized males into the wild. Once released, it is important to be able to distinguish the released males from the wild males for monitoring purposes. Several methods to mark the sterile males exist. However, most have limitations due to monetary, process efficiency, or insect quality. Aedes albopictus is naturally infected with Wolbachia at a high prevalence. Therefore, the elimination of Wolbachia can serve as a biomarker to distinguish the factory-reared male mosquitoes from wild conspecifics. RESULTS: In this study, a Wolbachia-free Ae. albopictus GT strain was developed and its fitness evaluated, which was found to be comparable to the wild GUA strain. In addition, GT male mosquitoes were irradiated at the adult stage and a dose of 20 Gy or more induced over 99% sterility. Moreover, a dose of 30 Gy (almost completely sterilizing male and female mosquitoes) had limited effects on the mating competitiveness of GT males and vector competence of GT females, respectively. However, radiation reduced mosquito longevity, regardless of its sex. CONCLUSION: Our results indicated that the Ae. albopictus GT strain can be distinguished from the wild mosquitoes based on Wolbachia status and shows similar fitness, radio-sensitivity and arbovirus susceptibility to the GUA strain, indicating that it is feasible to use the GT strain to suppress Ae. albopictus populations for SIT programmes. This article is protected by copyright. All rights reserved.
Modeling emergence of Wolbachia toxin-antidote protein functions with an evolutionary algorithm
26277J. Beckmann, J. Gillespie and D. Tauritz, Front Microbiol, 14:1116766. 2023-06-09 10:36:38.
Evolutionary algorithms (EAs) simulate Darwinian evolution and adeptly mimic natural evolution. Most EA applications in biology encode high levels of abstraction in top-down population ecology models. In contrast, our research merges protein alignment algorithms from bioinformatics into codon based EAs that simulate molecular protein string evolution from the bottom up. We apply our EA to reconcile a problem in the field of Wolbachia induced cytoplasmic incompatibility (CI). Wolbachia is a microbial endosymbiont that lives inside insect cells. CI is conditional insect sterility that operates as a toxin antidote (TA) system. Although, CI exhibits complex phenotypes not fully explained under a single discrete model. We instantiate in-silico genes that control CI, CI factors (cifs), as strings within the EA chromosome. We monitor the evolution of their enzymatic activity, binding, and cellular localization by applying selective pressure on their primary amino acid strings. Our model helps rationalize why two distinct mechanisms of CI induction might coexist in nature. We find that nuclear localization signals (NLS) and Type IV secretion system signals (T4SS) are of low complexity and evolve fast, whereas binding interactions have intermediate complexity, and enzymatic activity is the most complex. Our model predicts that as ancestral TA systems evolve into eukaryotic CI systems, the placement of NLS or T4SS signals can stochastically vary, imparting effects that might impact CI induction mechanics. Our model highlights how preconditions and sequence length can bias evolution of cifs toward one mechanism or another.
Molecular detection of reproductive symbionts and parthenogenesis experiments in Tuta absoluta from Argentina: facing potential for sustainable and specific pest control strategies
26184C. Cagnotti, C. Conte, J. Kramar, S. Lanzavecchia and S. López, Entomologia Experimentalis et Applicata, 2023-06-07 12:24:43.
Tomato leafminer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a key pest of tomato crops. Specific and environmentally friendly control strategies against this pest, such as the sterile insect technique (SIT), are under development and sexual reproduction has emerged as a key focal point to ensure its success. In the present study, we analyzed four representative T. absoluta populations from Argentina, focusing on the molecular detection of endosymbionts potentially associated with reproductive abnormalities and on determining whether parthenogenesis can occur under laboratory conditions. Larvae of T. absoluta were collected in commercial tomato plantations from La Plata and Mar del Plata (both in Buenos Aires province), Bella Vista (Corrientes province), and Yuto (Jujuy province). Tuta absoluta adults were evaluated by standard PCR for the presence of reproductive endosymbionts (Wolbachia sp., Spiroplasma sp., Arsenophonus sp., Cardinium sp., and Rickettsia sp.). For parthenogenesis assays, 20–23 virgin females from each T. absoluta geographic population were life-long isolated in Petri dishes with a tomato leaf. Fecundity, fertility, and female longevity were estimated and compared with results from mated females from each population. Our results showed the presence of a unique endosymbiont (Wolbachia sp. supergroup B, sequence type 41). Fecundity of the unmated females was significantly lower than fecundity of mated females in all T. absoluta populations. In addition, unmated females only laid infertile eggs. In conclusion, the absence of parthenogenesis in T. absoluta from representative geographic populations supports the implementation of SIT and mating disruption as effective control strategies against this pest in Argentina. © 2023 Netherlands Entomological Society.
Molecular Biology of Cytoplasmic Incompatibility Caused by Wolbachia Endosymbionts
25549M. Hochstrasser, Annual Review of Microbiology, 2023-06-07 08:38:45.
Among endosymbiotic bacteria living within eukaryotic cells, Wolbachia is exceptionally widespread, particularly in arthropods. Inherited through the female germline, it has evolved ways to increase the fraction of bacterially infected offspring by inducing parthenogenesis, feminization, male killing, or, most commonly, cytoplasmic incompatibility (CI). In CI, Wolbachia infection of males causes embryonic lethality unless they mate with similarly infected females, creating a relative reproductive advantage for infected females. A set of related Wolbachia bicistronic operons encodes the CI-inducing factors. The downstream gene encodes a deubiquitylase or nuclease and is responsible for CI induction by males, while the upstream product when expressed in females binds its sperm-introduced cognate partner and rescues viability. Both toxin-antidote and host-modification mechanisms have been proposed to explain CI. Interestingly, male killing by either Spiroplasma or Wolbachia endosymbionts involves deubiquitylases as well. Interference with the host ubiquitin system may therefore be a common theme among endosymbiont-mediated reproductive alterations.
Wolbachia -induced inhibition of O’nyong nyong virus in Anopheles mosquitoes is mediated by Toll signaling and modulated by cholesterol
26465S. Pujhari, G. L. Hughes, N. Pakpour, Y. Suzuki and J. L. Rasgon, bioRxiv, 10.1101/2023.05.31.543096. 2023-06-01 07:41:43.
Enhanced host immunity and competition for metabolic resources are two main competing hypotheses for the mechanism of Wolbachia -mediated pathogen inhibition in arthropods. Using an Anopheles mosquito - somatic Wolbachia infection - O'nyong nyong virus (ONNV) model, we demonstrate that the mechanism underpinning Wolbachia -mediated virus inhibition is up-regulation of the Toll innate immune pathway. However, the viral inhibitory properties of Wolbachia were abolished by cholesterol supplementation. This result was due to Wolbachia -dependent cholesterol-mediated suppression of Toll signaling rather than competition for cholesterol between Wolbachia and virus. The inhibitory effect of cholesterol was specific to Wolbachia -infected Anopheles mosquitoes and cells. These data indicate that both Wolbachia and cholesterol influence Toll immune signaling in Anopheles mosquitoes in a complex manner and provide a functional link between the host immunity and metabolic competition hypotheses for explaining Wolbachia -mediated pathogen interference in mosquitoes. In addition, these results provide a mechanistic understanding of the mode of action of Wolbachia -induced pathogen blocking in Anophelines, which is critical to evaluate the long-term efficacy of control strategies for malaria and Anopheles -transmitted arboviruses. HIGHLIGHTS: Wolbachia inhibits O'nyong nyong virus (ONNV) in Anopheles mosquitoes. Enhanced Toll signaling is responsible for Wolbachia -induced interference of ONNV. Cholesterol suppresses Toll signaling to modulate Wolbachia -induced ONNV interference.
An economic evaluation of Wolbachia deployments for dengue control in Vietnam
25418H. C. Turner, D. L. Quyen, R. Dias, P. T. Huong, C. P. Simmons and K. L. Anders, PLOS Neglected Tropical Diseases, 17:e0011356. 2023-05-30 07:56:11.
INTRODUCTION: Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the benefits of such an intervention at a large scale. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam-targeted at the highest burden urban areas. METHODS: Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). The effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases was assumed to be 75%. We assumed that the intervention would maintain this effectiveness for at least 20 years (but tested this assumption in the sensitivity analysis). A cost-utility analysis and cost-benefit analysis were conducted. RESULTS: From the health sector perspective, the Wolbachia intervention was projected to cost US$420 per disability-adjusted life year (DALY) averted. From the societal perspective, the overall cost-effectiveness ratio was negative, i.e. the economic benefits outweighed the costs. These results are contingent on the long-term effectiveness of Wolbachia releases being sustained for 20 years. However, the intervention was still classed as cost-effective across the majority of the settings when assuming only 10 years of benefits. CONCLUSION: Overall, we found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control
25203T. Matsufuji and S. Seirin-Lee, Journal of Theoretical Biology, 569:111519. 2023-05-29 09:18:33.
For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect technique (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wild-type female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control by replacement owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we develop a population-based IIT mathematical model using cytoplasmic incompatibility and evaluate the effectiveness of the IIT method in scenarios where contamination is present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluate the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect suppression of vector mosquito population regardless of contamination.
The prevalence of Wolbachia in multiple cockroach species and its implication for urban insect management
25869S. O. Oladipupo, Y. Laidoudi, J. F. Beckmann, X. P. Hu and A. G. Appel, Journal of Economic Entomology, 2023-05-29 08:56:29.
Cockroach management relies heavily on the use of conventional insecticides in urban settings, which no longer provide the anticipated level of control. Knowledge of cockroach endosymbionts, like Wolbachia, might provide novel avenues for control. Therefore, we screened 16 cockroach species belonging to 3 families (Ectobiidae, Blattidae, and Blaberidae) for the presence of Wolbachia. We mapped the evolution of Wolbachia-cockroach relationships based on maximum likelihood phylogeny and phylogenetic species clustering on a multi-loci sequence dataset (i.e., coxA, virD4, hcpA, and gatB) of Wolbachia genes. We confirmed the previous report of Wolbachia in 1 Ectobiid species; Supella longipalpa (Fab.), and detected the presence of Wolbachia in 2 Ectobiid species; Balta notulata (Stål) and Pseudomops septentrionalis Hebard, and 1 Blaberid species; Gromphadorhina portentosa (Schaum). All cockroach-associated Wolbachia herein detected were clustered with the ancestor of F clade Wolbachia of Cimex lectularius L. (bed bugs). Since Wolbachia provision C. lectularius with biotin vitamins that confer reproductive fitness, we screened the cockroach-associated Wolbachia for the presence of biotin genes. In toto, our results reveal 2 important findings: (i) Wolbachia is relatively uncommon among cockroach species infecting about 25% of species investigated, and (ii) cockroach-associated Wolbachia have biotin genes that likely provide nutritional benefits to their hosts. Thus, we discuss the potential of exploring Wolbachia as a tool for urban insect management.
Wolbachia protects Drosophila melanogaster against two naturally occurring and virulent viral pathogens
25211G. Bruner-Montero and F. M. Jiggins, Scientific Reports, 13:8518. 2023-05-25 13:38:46.
Wolbachia is a common endosymbiont that can protect insects against viral pathogens. However, whether the antiviral effects of Wolbachia have a significant effect on fitness remains unclear. We have investigated the interaction between Drosophila melanogaster, Wolbachia and two viruses that we recently isolated from wild flies, La Jolla virus (LJV; Iflaviridae) and Newfield virus (NFV; Permutotetraviridae). Flies infected with these viruses have increased mortality rates, and NFV partially sterilizes females. These effects on fitness were reduced in Wolbachia-infected flies, and this was associated with reduced viral titres. However, Wolbachia alone also reduces survival, and under our experimental conditions these costs of the symbiont can outweigh the benefits of antiviral protection. In contrast, protection against the sterilizing effect of NFV leads to a net benefit of Wolbachia infection after exposure to the virus. These results support the hypothesis that Wolbachia is an important defense against the natural pathogens of D. melanogaster. Furthermore, by reducing the cost of Wolbachia infection, the antiviral effects of Wolbachia may aid its invasion into populations and help explain why it is so common in nature.
Holobiont perspectives on tripartite interactions among microbiota, mosquitoes, and pathogens
25208R. Zheng, Q. Wang, R. Wu, P. N. Paradkar, A. A. Hoffmann and G. H. Wang, ISME, 2023-05-25 13:32:28.
Mosquito-borne diseases like dengue and malaria cause a significant global health burden. Unfortunately, current insecticides and environmental control strategies aimed at the vectors of these diseases are only moderately effective in decreasing disease burden. Understanding and manipulating the interaction between the mosquito holobiont (i.e., mosquitoes and their resident microbiota) and the pathogens transmitted by these mosquitoes to humans and animals could help in developing new disease control strategies. Different microorganisms found in the mosquito's microbiota affect traits related to mosquito survival, development, and reproduction. Here, we review the physiological effects of essential microbes on their mosquito hosts; the interactions between the mosquito holobiont and mosquito-borne pathogen (MBP) infections, including microbiota-induced host immune activation and Wolbachia-mediated pathogen blocking (PB); and the effects of environmental factors and host regulation on the composition of the microbiota. Finally, we briefly overview future directions in holobiont studies, and how these may lead to new effective control strategies against mosquitoes and their transmitted diseases.
Wolbachia genetically interacts with the bag of marbles germline stem cell gene in male D. melanogaster
26548M. Wenzel and C. F. Aquadro, MicroPubl Biol, 2023-05-25 08:57:31.
The bacterial endosymbiont Wolbachia manipulates reproduction of its arthropod hosts to promote its own maternal vertical transmission. In female D. melanogaster , Wolbachia has been shown to genetically interact with three key reproductive genes ( bag of marbles ( bam ) , Sex-lethal, and mei-P26) , as it rescues the reduced female fertility or fecundity phenotype seen in partial loss-of-function mutants of these genes . Here, we show that Wolbachia also partially rescues male fertility in D. melanogaster carrying a new, largely sterile bam allele when in a bam null genetic background. This finding shows that the molecular mechanism of Wolbachia 's influence on its hosts' reproduction involves interaction with genes in males as well as females, at least in D. melanogaster .
Combined actions of bacteriophage-encoded genes in Wolbachia-induced male lethality
25420H. Arai, H. Anbutsu, Y. Nishikawa, M. Kogawa, K. Ishii, M. Hosokawa, S. R. Lin, M. Ueda, M. Nakai, Y. Kunimi, T. Harumoto, D. Kageyama, H. Takeyama and M. N. Inoue, iScience, 26:106842. 2023-05-10 08:02:36.
Some Wolbachia endosymbionts induce male killing, whereby male offspring of infected females are killed during development; however, the origin and diversity of the underlying mechanisms remain unclear. In this study, we identified a 76 kbp prophage region specific to male-killing Wolbachia hosted by the moth Homona magnanima. The prophage encoded a homolog of the male-killing gene oscar in Ostrinia moths and the wmk gene that induces various toxicities in Drosophila melanogaster. Upon overexpressing these genes in D. melanogaster, wmk-1 and wmk-3 killed all males and most females, whereas Hm-oscar, wmk-2, and wmk-4 had no impact on insect survival. Strikingly, co-expression of tandemly arrayed wmk-3 and wmk-4 killed 90% of males and restored 70% of females, suggesting their conjugated functions for male-specific lethality. While the male-killing gene in the native host remains unknown, our findings highlight the role of bacteriophages in male-killing evolution and differences in male-killing mechanisms among insects.
Wolbachia-based strategies for control of agricultural pests
25104J. T. Gong, T. P. Li, M. K. Wang and X. Y. Hong, Curr Opin Insect Sci, 101039:10.1016/j.cois.2023.101039. 2023-04-25 10:26:15.
Wolbachia-based incompatible insect technique (IIT) and pathogen blocking technique (PBT) have been shown to be effective at protecting humans from mosquito-borne diseases in the past decades. Population suppression based on IIT and population replacement based on PBT have become major field application strategies that have continuously been improved by the translational research on Wolbachia-transinfected mosquitoes. Similarly, Wolbachia-based approaches have been proposed for the protection of plants from agricultural pests and their associated diseases. However, a bottleneck in Wolbachia-based strategies for the control of agricultural pests is the need for methods to establish Wolbachia-transinfected insect lines. As a first step in this direction, we compare field control strategies for mosquitos with the potential strategies for agricultural pests based on Wolbachia. Our results show that there is a critical need for establishing productive insect lines and accumulating field test data.
Massive mosquito factory in Brazil aims to halt dengue
24984M. Lenharo, Nature, 2023-04-14 09:48:56.
The non-profit World Mosquito Program (WMP) has announced that it will release modified mosquitoes in many of Brazil’s urban areas over the next 10 years, with the aim of protecting up to 70 million people from diseases such as dengue. Researchers have tested the release of this type of mosquito — which carries a Wolbachia bacterium that stops the insect from transmitting viruses — in select cities in countries such as Australia, Brazil, Colombia, Indonesia and Vietnam. But this will be the first time that the technology is dispersed nationwide. A mosquito factory will be built in a location yet to be determined in Brazil to supply the WMP’s ambitious initiative, in partnership with the Oswaldo Cruz Foundation (Fiocruz), a Brazilian public science institution in Rio de Janeiro. The facility should begin operating in 2024 and will produce up to five billion mosquitoes per year. “This will be the biggest facility in the world” to produce Wolbachia-infected mosquitoes, says Scott O’Neill, a microbiologist at Monash University in Melbourne, Australia, and head of the WMP. “And it will allow us in a short period of time to cover more people than in any other country.” Brazil has one of the highest rates of dengue infection in the world, reporting more than two million cases in 2022.Despite the positive results from past mosquito releases, researchers expect that it will be challenging to operate the technology at such a massive scale.
Dengue Exposure and Wolbachia wMel Strain Affects the Fertility of Quiescent Eggs of Aedes aegypti
25102M. T. Petersen, D. Couto-Lima, G. A. Garcia, M. G. Pavan, M. R. David and R. Maciel-de-Freitas, Viruses, 15. 2023-04-12 10:20:54.
(1) Background: The deployment of the bacterium Wolbachia to reduce arbovirus transmission is ongoing in several countries worldwide. When Wolbachia-carrying Aedes aegypti are released and established in the field, females may feed on dengue-infected hosts. The effects of simultaneous exposure on life-history traits of Ae. aegypti to Wolbachia wMel strain and dengue-1 virus DENV-1 remain unclear. (2) Methods: We monitored 4 groups (mosquitoes with either DENV-1 or Wolbachia, coinfected with DENV-1 and Wolbachia, as well as negative controls) to estimate Ae. aegypti survival, oviposition success, fecundity, collapsing and fertility of quiescent eggs for 12 weeks. (3) Results: Neither DENV-1 nor Wolbachia had a significant impact on mosquito survival nor on mosquito fecundity, although the last parameter showed a tendency to decrease with ageing. There was a significant decrease in oviposition success in individuals carrying Wolbachia. Wolbachia infection and storage time significantly increased egg collapse parameter on the egg viability assay, while DENV-1 had a slight protective effect on the first four weeks of storage. (4) Conclusions: Despite limitations, our results contribute to better understanding of the tripartite interaction of virus, bacteria and mosquito that may take place in field conditions and aid in guaranteeing the Wolbachia strategy success.
Spatial Distribution and Long-Term Persistence of Wolbachia-Infected Aedes aegypti in the Mentari Court, Malaysia
25100Y. L. Cheong, W. A. Nazni, H. L. Lee, A. NoorAfizah, I. C. MohdKhairuddin, G. M. R. Kamarul, N. M. N. Nizam, M. A. K. Arif, Z. M. NurZatilAqmar, S. M. Irwan, K. Khadijah, Y. M. Paid, O. Topek, A. H. Hasnor, R. AbuBakar, B. Singh Gill, K. Fadzilah, A. Tahi, Insects, 14. 2023-04-11 10:16:44.
Dengue is endemic in Malaysia, and vector control strategies are vital to reduce dengue transmission. The Wolbachia strain wAlbB carried by both sexes of Ae. aegypti was released in Mentari Court, a high-rise residential site, in October 2017 and stopped after 20 weeks. Wolbachia frequencies are still being monitored at multiple traps across this site, providing an opportunity to examine the spatiotemporal distribution of Wolbachia and mosquito density with respect to year, residential block, and floor, using spatial interpolation in ArcGIS, GLMs, and contingency analyses. In just 12 weeks, Wolbachia-infected mosquitoes were established right across the Mentari Court site with an overall infection frequency of >90%. To date, the Wolbachia frequency of Ae. aegypti has remained high in all areas across the site despite releases finishing four years ago. Nevertheless, the Wolbachia invaded more rapidly in some residential blocks than others, and also showed a relatively higher frequency on the eighth floor. The Ae. aegypti index tended to differ somewhat between residential blocks, whilst the Ae. albopictus index was relatively higher at the top and bottom floors of buildings. In Mentari Court, only a short release period was required to infiltrate Wolbachia completely and stably into the natural population. The results inform future releases in comparable sites in a dengue control programme.
A bacterium against the tiger: further evidence of the potential of non-inundative releases of males with manipulated Wolbachia infection in reducing fertility of Aedes albopictus field populations in Italy
24966B. Caputo, R. Moretti, C. Virgillito, M. Manica, E. Lampazzi, G. Lombardi, P. Serini, V. Pichler, N. W. Beebe, A. Della Torre and M. Calvitti, Pest Management Science, 2023-04-06 10:42:30.
BACKGROUND: Incompatible Insect Technique (IIT) is a population suppression approach based on the release of males with manipulated Wolbachia infection inducing egg inviability in wild females. We here present results of multiple field releases of incompatible ARwP males carried out in 2019 in a 2.7-ha green area within urban Rome (Italy) to assess the effect on Ae. albopictus egg viability. Data are compared with results obtained in 2018, when the approach was tested for the first time in Europe. RESULTS: An average of 4,674 ARwP males were released weekly for 7 weeks, resulting in a mean ARwP/wild male ratio of 1.1:1 (versus 0.7:1 in 2018). Egg-viability dynamics in ovitraps significantly varied between Treated and Control Sites, with an estimated overall reduction of 35% (versus 15% in 2018). The estimated proportion of females classified as mated with ARwP males was 41.8% and the viability rate of eggs laid by these females (9.5%) was on average significantly lower than that of females only mated with wild males (87.8%); however, high variability in fertility was observed. Values of ARwP male competitiveness were 0.36 and 0.73 based on the overall viability rate of eggs in ovitraps and on female fertility, respectively, i.e. well above the conventional 0.2 threshold for an effective suppressive impact in the field. CONCLUSIONS: Results further support the potential of IIT as a tool to contribute to Ae. albopictus control in the urban context, stressing the need of larger field trials to evaluate the cost-efficacy of the approach in temperate regions.
One strain may hide another: Cryptic male-killing Wolbachia
24924E. A. Hornett and G. D. D. Hurst, PLOS Biology, 21:e3002076. 2023-03-30 13:44:51.
While heritable symbionts are common in insects, strains that act as male-killers are considered rare. This Primer explores a new study in PLOS Biology which reveals a novel male-killer hidden by co-infection and host resistance, highlighting the complexity of host-microbial interactions in natural systems.
The Wolbachia WalE1 effector alters Drosophila endocytosis
24855M. Martin and I. L. G. Newton, bioRxiv, 2023-03-27 15:30:37.
The most common intracellular bacterial infection is Wolbachia pipientis , a microbe that manipulates host reproduction and is used in control of insect vectors. Phenotypes induced by Wolbachia have been studied for decades and range from sperm-egg incompatibility to male killing. How Wolbachia alters host biology is less well understood. Previously, we characterized the first Wolbachia effector â€" WalE1, which encodes a synuclein domain at the N terminus. Purified WalE1 sediments with and bundles actin and when heterologously expressed in flies, increases Wolbachia titer in the developing oocyte. In this work, we first identify the native expression WalE1 by Wolbachia infecting both fly cells and whole animals. WalE1 appears as aggregates, separate from Wolbachia cells. We next show that WalE1 co-immunoprecipitates with the host protein Past1 and that WalE1 manipulates host endocytosis. Yeast expressing WalE1 show deficiency in uptake of FM4-64 dye, and flies harboring mutations in Past1 or overexpressing WalE1 are sensitive to AgNO (3) , a hallmark of endocytosis defects. Finally, we also show that Past1 null flies harbor more Wolbachia overall and in late egg chambers. Our results identify interactions between a Wolbachia secreted effector and a host protein and point to yet another important host cell process impinged upon by Wolbachia .
Modelling Emergence of Wolbachia Toxin-Antidote Protein Functions with an Evolutionary Algorithm
24926J. Beckmann, J. Gillespie and D. Tauritz, bioRxiv, 2023-03-25 13:50:46.
Evolutionary algorithms (EAs) simulate Darwinian evolution and adeptly mimic natural evolution. Most EA applications in biology encode high levels of abstraction in top-down ecological population models. In contrast, our research merges protein alignment algorithms from bioinformatics into codon based EAs that simulate molecular protein string evolution from the bottom up. We apply our EA to reconcile a problem in the field of Wolbachia induced cytoplasmic incompatibility (CI). Wolbachia is a microbial endosymbiont that lives inside insect cells. CI is conditional insect sterility that operates as a toxin antidote (TA) system. Although, CI exhibits complex phenotypes not fully explained under a single discrete model. We instantiate in-silico genes that control CI, CI factors ( cifs ), as strings within the EA chromosome. We monitor the evolution of their enzymatic activity, binding, and cellular localization by applying selective pressure on their primary amino acid strings. Our model helps rationalize why two distinct mechanisms of CI induction might coexist in nature. We find that nuclear localization signals (NLS) and Type IV secretion system signals (T4SS) are of low complexity and evolve fast, whereas binding interactions have intermediate complexity, and enzymatic activity is the most complex. Our model predicts that as ancestral TA systems evolve into eukaryotic CI systems, the placement of NLS or T4SS signals can stochastically vary, imparting effects that might impact CI induction mechanics. Our model highlights how preconditions, genetic diversity, and sequence length can bias evolution of cifs towards one mechanism or another.
A male-killing Wolbachia endosymbiont is concealed by another endosymbiont and a nuclear suppressor
24920K. M. Richardson, P. A. Ross, B. S. Cooper, W. R. Conner, T. Schmidt and A. A. Hoffmann, PLoS Biol, 21:e3001879. 2023-03-22 13:30:17.
Bacteria that live inside the cells of insect hosts (endosymbionts) can alter the reproduction of their hosts, including the killing of male offspring (male killing, MK). MK has only been described in a few insects, but this may reflect challenges in detecting MK rather than its rarity. Here, we identify MK Wolbachia at a low frequency (around 4%) in natural populations of Drosophila pseudotakahashii. MK Wolbachia had a stable density and maternal transmission during laboratory culture, but the MK phenotype which manifested mainly at the larval stage was lost rapidly. MK Wolbachia occurred alongside a second Wolbachia strain expressing a different reproductive manipulation, cytoplasmic incompatibility (CI). A genomic analysis highlighted Wolbachia regions diverged between the 2 strains involving 17 genes, and homologs of the wmk and cif genes implicated in MK and CI were identified in the Wolbachia assembly. Doubly infected males induced CI with uninfected females but not females singly infected with CI-causing Wolbachia. A rapidly spreading dominant nuclear suppressor genetic element affecting MK was identified through backcrossing and subsequent analysis with ddRAD SNPs of the D. pseudotakahashii genome. These findings highlight the complexity of nuclear and microbial components affecting MK endosymbiont detection and dynamics in populations and the challenges of making connections between endosymbionts and the host phenotypes affected by them.
Convergent Aedes and Drosophila CidB interactomes suggest cytoplasmic incompatibility targets are conserved
24875S. O. Oladipupo, J. D. Carroll and J. F. Beckmann, Insect Biochem Mol Biol, 103931. 2023-03-20 08:18:16.
Wolbachia-mediated cytoplasmic incompatibility (CI) is a conditional embryonic lethality induced when Wolbachia-modified sperm fertilizes an uninfected egg. The Wolbachia proteins, CidA and CidB control CI. CidA is a rescue factor that reverses lethality. CidA binds to CidB. CidB contains a deubiquitinating enzyme and induces CI. Precisely how CidB induces CI and what it targets are unknown. Likewise, how CidA prevents sterilization by CidB is not clear. To identify CidB substrates in mosquitos we conducted pull-down assays using recombinant CidA and CidB mixed with Aedes aegypti lysates to identify the protein interactomes of CidB and the CidB/CidA protein complex. Our data allow us to cross compare CidB interactomes across taxa for Aedes and Drosophila. Our data replicate several convergent interactions, suggesting that CI targets conserved substrates across insects. Our data support a hypothesis that CidA rescues CI by tethering CidB away from its substrates. Specifically, we identify ten convergent candidate substrates including P32 (protamine-histone exchange factor), karyopherin alpha, ubiquitin-conjugating enzyme, and bicoid stabilizing factor. Future analysis on how these candidates contribute to CI will clarify mechanisms.
Enhancing the scalability of Wolbachia-based vector-borne disease management: time and temperature limits for storage and transport of Wolbachia-infected Aedes aegypti eggs for field releases
24877M. J. Allman, Y. H. Lin, D. A. Joubert, J. Addley-Cook, M. C. Mejía-Torres, C. P. Simmons, H. A. Flores and J. E. Fraser, Parasit Vectors, 16:108. 2023-03-18 08:18:24.
BACKGROUND: Introgression of the bacterial endosymbiont Wolbachia into Aedes aegypti populations is a biocontrol approach being used to reduce arbovirus transmission. This requires mass release of Wolbachia-infected mosquitoes. While releases have been conducted using a variety of techniques, egg releases, using water-soluble capsules containing mosquito eggs and larval food, offer an attractive method due to its potential to reduce onsite resource requirements. However, optimisation of this approach is required to ensure there is no detrimental impact on mosquito fitness and to promote successful Wolbachia introgression. METHODS: We determined the impact of storage time and temperature on wild-type (WT) and Wolbachia-infected (wMel or wAlbB strains) Ae. aegypti eggs. Eggs were stored inside capsules over 8 weeks at 18 °C or 22 °C and hatch rate, emergence rate and Wolbachia density were determined. We next examined egg quality and Wolbachia density after exposing eggs to 4-40 °C to determine how eggs may be impacted if exposed to extreme temperatures during shipment. RESULTS: Encapsulating eggs for 8 weeks did not negatively impact egg viability or resulting adult emergence and Wolbachia density compared to controls. When eggs were exposed to temperatures within 4-36 °C for 48 h, their viability and resulting adult Wolbachia density were maintained; however, both were significantly reduced when exposed to 40 °C. CONCLUSIONS: We describe the time and temperature limits for maintaining viability of Wolbachia-infected Ae. aegypti eggs when encapsulated or exposed to extreme temperatures. These findings could improve the efficiency of mass releases by providing transport and storage constraints to ensure only high-quality material is utilised during field releases.
Functional analysis of Wolbachia Cid effectors unravels cooperative interactions to target host chromatin during replication
24869K. Terretaz, B. Horard, M. Weill, B. Loppin and F. Landmann, PLOS Pathogens, 19:e1011211. 2023-03-16 08:02:08.
Wolbachia are common bacteria among terrestrial arthropods. These endosymbionts transmitted through the female germline manipulate their host reproduction through several mechanisms whose most prevalent form called Cytoplasmic Incompatibility -CI- is a conditional sterility syndrome eventually favoring the infected progeny. Upon fertilization, the sperm derived from an infected male is only compatible with an egg harboring a compatible Wolbachia strain, this sperm leading otherwise to embryonic death. The Wolbachia Cif factors CidA and CidB responsible for CI and its neutralization function as a Toxin-Antitoxin system in the mosquito host Culex pipiens. However, the mechanism of CidB toxicity and its neutralization by the CidA antitoxin remain unexplored. Using transfected insect cell lines to perform a structure-function analysis of these effectors, we show that both CidA and CidB are chromatin interactors and CidA anchors CidB to the chromatin in a cell-cycle dependent-manner. In absence of CidA, the CidB toxin localizes to its own chromatin microenvironment and acts by preventing S-phase completion, independently of its deubiquitylase -DUB- domain. Experiments with transgenic Drosophila show that CidB DUB domain is required together with CidA during spermatogenesis to stabilize the CidA-CidB complex. Our study defines CidB functional regions and paves the way to elucidate the mechanism of its toxicity.
Distinct Wolbachia localization patterns in oocytes of diverse host species reveal multiple strategies of maternal transmission
24853Y. A. Radousky, M. T. J. Hague, S. Fowler, E. Paneru, A. Codina, C. Rugamas, G. Hartzog, B. S. Cooper and W. Sullivan, Genetics, 2023-03-13 15:24:48.
A broad array of endosymbionts radiate through host populations via vertical transmission, yet much remains unknown concerning the cellular basis, diversity and routes underlying this transmission strategy. Here we address these issues, by examining the cellular distributions of Wolbachia strains that diverged up to 50 million years ago in the oocytes of 18 divergent Drosophila species. This analysis revealed three Wolbachia distribution patterns: 1) a tight clustering at the posterior pole plasm (the site of germline formation); 2) a concentration at the posterior pole plasm, but with a significant bacteria population distributed throughout the oocyte; 3) and a distribution throughout the oocyte, with none or very few located at the posterior pole plasm. Examination of this latter class indicates Wolbachia accesses the posterior pole plasm during the interval between late oogenesis and the blastoderm formation. We also find that one Wolbachia strain in this class concentrates in the posterior somatic follicle cells that encompass the pole plasm of the developing oocyte. In contrast, strains in which Wolbachia concentrate at the posterior pole plasm generally exhibit no or few Wolbachia in the follicle cells associated with the pole plasm. Taken together, these studies suggest that for some Drosophila species, Wolbachia invade the germline from neighboring somatic follicle cells. Phylogenomic analysis indicates that closely related Wolbachia strains tend to exhibit similar patterns of posterior localization, suggesting that specific localization strategies are a function of Wolbachia-associated factors. Previous studies revealed that endosymbionts rely on one of two distinct routes of vertical transmission: continuous maintenance in the germline (germline-to-germline) or a more circuitous route via the soma (germline-to-soma-to-germline). Here we provide compelling evidence that Wolbachia strains infecting Drosophila species maintain the diverse arrays of cellular mechanisms necessary for both of these distinct transmission routes. This characteristic may account for its ability to infect and spread globally through a vast range of host insect species.
First report of natural Wolbachia infections in mosquitoes from Cuba
24933A. Ruiz, G. Gutiérrez-Bugallo, R. Rodríguez-Roche, L. Pérez, R. González-Broche, L. A. Piedra, L. C. Martínez, Z. Menéndez, A. Vega-Rúa and J. A. Bisset, Acta Tropica, 242:106891. 2023-03-11 08:20:20.
Mosquitoes are extensively responsible for the transmission of pathogens. Novel strategies using Wolbachia could transform that scenario, since these bacteria manipulate mosquito reproduction, and can confer a pathogen transmission-blocking phenotype in culicids. Here, we screened the Wolbachia surface protein region by PCR in eight Cuban mosquito species. We confirmed the natural infections by sequencing and assessed the phylogenetic relationships among the Wolbachia strains detected. We identified four Wolbachia hosts: Aedes albopictus, Culex quinquefasciatus, Mansonia titillans, and Aedes mediovittatus (first report worldwide). Knowledge of Wolbachia strains and their natural hosts is essential for future operationalization of this vector control strategy in Cuba.
Modeling Sustained Transmission of Wolbachia among Anopheles Mosquitoes: Implications for Malaria Control in Haiti
24916D. Florez, A. J. Young, K. J. Bernabé, J. M. Hyman and Z. Qu, Trop Med Infect Dis, 8. 2023-03-09 12:09:17.
Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We developed and analyzed a mechanistic compartmental ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derive and interpret dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents a backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at baseline. We simulate different intervention scenarios, including prerelease mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release times of the year. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the prerelease mitigation process. Moreover, the model predicts that it is more efficient to release during the dry season than the wet season.
A mosquito population suppression model with a saturated Wolbachia release strategy in seasonal succession
24814Z. Zhang, L. Chang, Q. Huang, R. Yan and B. Zheng, J Math Biol, 86:51. 2023-03-06 08:55:06.
Releasing Wolbachia-infected male mosquitoes to suppress wild female mosquitoes through cytoplasmic incompatibility has shown great promise in controlling and preventing mosquito-borne diseases. To make the release logistically and economically feasible, we propose a saturated release strategy, which is only implemented during the epidemic season of mosquito-borne diseases. Under this assumption, the model becomes a seasonally switching ordinary differential equation model. The seasonal switch brings rich dynamics, including the existence of a unique periodic solution or exactly two periodic solutions, which are proved by using the qualitative property of the Poincaré map. Sufficient conditions are also obtained for determining the stability of the periodic solutions.
Analysing inhibition of dengue virus in Wolbachia-infected mosquito cells following the removal of Wolbachia
24822M. Hussain, K. Etebari and S. Asgari, Virology, 581:48-55. 2023-03-03 10:30:05.
Wolbachia pipientis is known to block replication of positive sense RNA viruses. Previously, we created an Aedes aegypti Aag2 cell line (Aag2.wAlbB) transinfected with the wAlbB strain of Wolbachia and a matching tetracycline-cured Aag2.tet cell line. While dengue virus (DENV) was blocked in Aag2.wAlbB cells, we found significant inhibition of DENV in Aag2.tet cells. RNA-Seq analysis of the cells confirmed removal of Wolbachia and lack of expression of Wolbachia genes that could have been due to lateral gene transfer in Aag2.tet cells. However, we noticed a substantial increase in the abundance of phasi charoen-like virus (PCLV) in Aag2.tet cells. When RNAi was used to reduce the PCLV levels, DENV replication was significantly increased. Further, we found significant changes in the expression of antiviral and proviral genes in Aag2.tet cells. Overall, the results reveal an antagonistic interaction between DENV and PCLV and how PCLV-induced changes could contribute to DENV inhibition.
Effects of Wolbachia on Transposable Element Expression Vary Between Drosophila melanogaster Host Genotypes
24871A. T. Eugénio, M. S. P. Marialva and P. Beldade, Genome Biology Evolution, 15. 2023-03-03 08:07:31.
Transposable elements (TEs) are repetitive DNA sequences capable of changing position in host genomes, thereby causing mutations. TE insertions typically have deleterious effects but they can also be beneficial. Increasing evidence of the contribution of TEs to adaptive evolution further raises interest in understanding what factors impact TE activity. Based on previous studies associating the bacterial endosymbiont Wolbachia with changes in the abundance of piRNAs, a mechanism for TE repression, and to transposition of specific TEs, we hypothesized that Wolbachia infection would interfere with TE activity. We tested this hypothesis by studying the expression of 14 TEs in a panel of 25 Drosophila melanogaster host genotypes, naturally infected with Wolbachia and annotated for TE insertions. The host genotypes differed significantly in Wolbachia titers inside individual flies, with broad-sense heritability around 20%, and in the number of TE insertions, which depended greatly on TE identity. By removing Wolbachia from the target host genotypes, we generated a panel of 25 pairs of Wolbachia-positive and Wolbachia-negative lines in which we quantified transcription levels for our target TEs. We found variation in TE expression that was dependent on Wolbachia status, TE identity, and host genotype. Comparing between pairs of Wolbachia-positive and Wolbachia-negative flies, we found that Wolbachia removal affected TE expression in 21.1% of the TE-genotype combinations tested, with up to 2.3 times differences in the median level of transcript. Our data show that Wolbachia can impact TE activity in host genomes, underscoring the importance this endosymbiont can have in the generation of genetic novelty in hosts.
Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes
27978D. Thi Hue Kien, K. Edenborough, D. da Silva Goncalves, T. Thuy Vi, E. Casagrande, H. Thi Le Duyen, V. Thi Long, L. Thi Dui, V. Thi Tuyet Nhu, N. Thi Giang, H. Thi Xuan Trang, E. Lee, I. a. Donovan-Banfield, H. Thi Thuy Van, N. Minh Nguyet, N. Thanh Phong, Virus Evolution, 9:vead016. 2023-03-03 07:47:19.
The introgression of antiviral strains of Wolbachia into Aedes aegypti mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of Wolbachia and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in Ae. aegypti mosquitoes infected with the wMel strain of Wolbachia. Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in wMel-infected Ae. aegypti than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These findings provide proof of concept that wMel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether wMel imparts selective pressure on DENV evolution in locations where wMel is established.
Wolbachia pipientis infections in populations of Aedes albopictus in the city of València (Spain): implications for mosquito control
24830R. Bueno-Marí, R. Domínguez-Santos, M. Trelis, E. Garrote-Sánchez, M. Cholvi, F. Quero de Lera, M. Khoubbane, A. Marcilla and R. Gi, Revista Española de Salud Pública, 97. 2023-03-02 16:20:52.
OBJECTIVE: The presence of Aedes albopictus, of high sanitary and social impact, was first reported in Valencia (Eastern Spain) in 2015. Innovative tools for its control include the use of the endosymbiotic bacterium Wolbachia pipientis. The release of mosquito males infected with the wPip strain, has proven very promising for large-scale Incompatible Insect Technique (IIT) applications. Before this strategy can be implemented in Valencia, it is important to know whether the natural local mosquito populations are Wolbachia-infected and, if so, identifying the infecting strains/supergroups, these being the objectives of the present work. METHODS: Eggs were collected from the 19 districts of the València city between May and October 2019. A total of 50 lab-reared adult Ae. albopictus individuals were processed and analyzed for Wolbachia detection and molecular characterization. These actions took place within the framework of a collaboration established with the Department of Health and Consumer Affairs of the city council of Valencia. Fisher's exact test was used to detect the statistical significance of the differences between groups. RESULTS: Our study revealed that 94% of the analyzed samples were naturally infected with Wolbachia. Both wAlbA and wAlbB supergroups were identified, with most samples (72% of the infected ones) carrying co-infections. CONCLUSIONS: These data provide the first characterization of the Wolbachia presence in natural populations of Ae. albopictus in the Mediterranean area of Spain. This information is relevant to evaluate the potential use of Wolbachia strains in order to achieve the suppression of the Asian tiger mosquito populations through massive release of artificially-infected males.
Satellite Rearing of Aedes Mosquito Eggs: Synchronized Empirical Test of a Novel Mass Rearing Model
24981K. L. Dobson, K. Blore, J. A. Henke, K. Y. Hung, T. Morgan, T. Posey, S. Sun, O. Sypes, N. P. Tremblay and S. L. Dobson, J Am Mosq Control Assoc, 39:12-17. 2023-03-01 09:41:35.
Mosquito suppression strategies based on "rear and release" of male mosquitoes are attracting renewed interest from governments, municipalities, and private businesses. These include irradiation-based sterile insect technique, Wolbachia-based technologies, and genetic modification. Each of these approaches requires the mass rearing and release of adult male mosquitoes, which typically is accomplished via a rearing facility near the release site. Although some release programs have relied on centralized rearing and shipment of adult males, adult male mosquitoes are relatively fragile, and their fitness can be diminished by temperature fluctuations, humidity, nutritional deficiencies, and other stresses that occur during shipment. Furthermore, expensive, expedited shipment is typically used to maximize the amount of adult lifetime in the field following the release. In contrast, Aedes aegypti and Ae. albopictus eggs can be desiccated and stored for long periods. They are small, and many millions of eggs can be shipped without specialized environmental conditions and using less expensive means. Here we examine a model in which mosquito eggs are centrally produced and then mailed to satellite rearing facilities. As a control, a replicate set of eggs was reared at the factory of origin. At each of the rearing sites, cloud-based software was used to track and compare rearing at the different locations. The results demonstrate similar rearing outcomes (i.e., egg hatch, immature development, and number of adult males) at each of the different sites for both species. We discuss the outcome in relation to downstream applications and potential future studies.
Ovarian Transcriptional Response to Wolbachia Infection in D. melanogaster in the Context of Between-Genotype Variation in Gene Expression
24807S. I. Frantz, C. M. Small, W. A. Cresko and N. D. Singh, G3-Genes Genomes Genetics, 2023-03-01 08:37:16.
Wolbachia is a maternally-transmitted endosymbiotic bacteria that infects a wide variety of arthropod and nematode hosts. The effects of Wolbachia on host biology are far-reaching and include changes in host gene expression. However, previous work on the host transcriptional response has generally been investigated in the context of a single host genotype. Thus, the relative effect of Wolbachia infection versus host genotype on gene expression is unknown. Here we explicitly test the relative roles of Wolbachia infection and host genotype on host gene expression by comparing the ovarian transcriptomes of four strains of D. melanogaster infected and uninfected with Wolbachia. Our data suggest that infection explains a small amount of transcriptional variation, particularly in comparison to variation in gene expression among strains. However, infection specifically affects genes related to cell cycle, translation, and metabolism. We also find enrichment of cell division and recombination processes among genes with infection-associated differential expression. Broadly, the transcriptomic changes identified in this study provide novel understanding of the relative magnitude of the effect of Wolbachia infection on gene expression in the context of host genetic variation, and also point to genes that are consistently differentially expressed in response to infection among multiple genotypes.
Wbm0076, a candidate effector protein of the Wolbachia endosymbiont of Brugia malayi, disrupts eukaryotic actin dynamics
24745M. K. Mills, L. G. McCabe, E. M. Rodrigue, K. F. Lechtreck and V. J. Starai, PLoS Pathogens, 19:e1010777. 2023-02-17 18:26:34.
Brugia malayi, a parasitic roundworm of humans, is colonized by the obligate intracellular bacterium, Wolbachia pipientis. The symbiosis between this nematode and bacterium is essential for nematode reproduction and long-term survival in a human host. Therefore, identifying molecular mechanisms required by Wolbachia to persist in and colonize B. malayi tissues will provide new essential information regarding the basic biology of this endosymbiosis. Wolbachia utilize a Type IV secretion system to translocate so-called "effector" proteins into the cytosol of B. malayi cells to promote colonization of the eukaryotic host. However, the characterization of these Wolbachia secreted proteins has remained elusive due to the genetic intractability of both organisms. Strikingly, expression of the candidate Wolbachia Type IV-secreted effector protein, Wbm0076, in the surrogate eukaryotic cell model, Saccharomyces cerevisiae, resulted in the disruption of the yeast actin cytoskeleton and inhibition of endocytosis. Genetic analyses show that Wbm0076 is a member of the family of Wiskott-Aldrich syndrome proteins (WAS [p]), a well-conserved eukaryotic protein family required for the organization of actin skeletal structures. Thus, Wbm0076 likely plays a central role in the active cell-to-cell movement of Wolbachia throughout B. malayi tissues during nematode development. As most Wolbachia isolates sequenced to date encode at least partial orthologs of wBm0076, we find it likely that the ability of Wolbachia to directly manipulate host actin dynamics is an essential requirement of all Wolbachia endosymbioses, independent of host cell species.
NDUFA8 potentially rescues Wolbachia-induced cytoplasmic incompatibility in Laodelphax striatellus
24743J. Chen, M. K. Wang, Q. X. Xie, X. L. Bing, T. P. Li and X. Y. Hong, Insect Sci, 2023-02-06 18:20:35.
The endosymbiont Wolbachia manipulates host reproduction by several strategies, one of the most important of which is cytoplasmic incompatibility (CI). CI can be rescued when Wolbachia-infected (WI) males mate with females infected with the same Wolbachia strain. However, the potential rescue mechanism of CI in the small brown planthopper Laodelphax striatellus is unclear. In this study, comparative transcriptome analysis was applied to explore the effect of Wolbachia on L. striatellus eggs. A total of 1387 differentially expressed genes were identified. RNAi of seven Wolbachia-upregulated key planthopper genes reduced egg reproduction, suggesting that Wolbachia might improve fecundity in L. striatellus by affecting these seven genes. Suppressing the expression of another upregulated gene, NDUFA8 (encoding NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8-like) by RNAi significantly increased the mortality of early embryos without affecting the number of deposited eggs. Wolbachia infection upregulated the mRNA level of NDUFA8, and dsNDUFA8 treatment of WI females re-created CI-like symptoms, suggesting that NDUFA8 is associated with the rescue phenotype. Because all L. striatellus populations worldwide are infected with Wolbachia, NDUFA8 is a potential pest control target. This article is protected by copyright. All rights reserved.
Investigating Wolbachia symbiont-mediated host protection against a bacterial pathogen using a natural Wolbachia nuclear insert
24740C. Prigot-Maurice, B. Lheraud, S. Guéritault, S. Beltran-Bech, R. Cordaux, J. Peccoud and C. Braquart-Varnier, Journal of Invertebrate Pathology, 197:107893. 2023-02-06 18:15:04.
Wolbachia bacterial endosymbionts provide protection against pathogens in various arthropod species but the underlying mechanisms remain misunderstood. By using a natural Wolbachia nuclear insert (f-element) in the isopod Armadillidium vulgare, we explored whether Wolbachia presence is mandatory to observe protection in this species or the presence of its genes is sufficient. We assessed survival of closely related females carrying or lacking the f-element (and lacking Wolbachia) challenged with the bacterial pathogen Salmonella enterica. Despite marginal significant effects, the f-element alone did not appear to confer survival benefits to its host, suggesting that Wolbachia presence in cells is crucial for protection.
Pangenomic analysis of Wolbachia provides insight into the evolution of host adaptation and cytoplasmic incompatibility factor genes
24785B. Liu, Y. S. Ren, C. Y. Su, Y. Abe and D. H. Zhu, Frontiers in Microbiology, 14:1084839. 2023-02-03 09:44:36.
INTRODUCTION: The genus Wolbachia provides a typical example of intracellular bacteria that infect the germline of arthropods and filarial nematodes worldwide. Their importance as biological regulators of invertebrates, so it is particularly important to study the evolution, divergence and host adaptation of these bacteria at the genome-wide level. METHODS: Here, we used publicly available Wolbachia genomes to reconstruct their evolutionary history and explore their adaptation under host selection. RESULTS: Our findings indicate that segmental and single-gene duplications, such as DNA methylase, bZIP transcription factor, heat shock protein 90, in single monophyletic Wolbachia lineages (including supergroups A and B) may be responsible for improving the ability to adapt to a broad host range in arthropod-infecting strains. In contrast to A strains, high genetic diversity and rapidly evolving gene families occur in B strains, which may promote the ability of supergroup B strains to adapt to new hosts and their large-scale spreading. In addition, we hypothesize that there might have been two independent horizontal transfer events of cif genes in two sublineages of supergroup A strains. Interestingly, during the independent evolution of supergroup A and B strains, the rapid evolution of cif genes in supergroup B strains resulted in the loss of their functional domain, reflected in a possible decrease in the proportion of induced cytoplasmic incompatibility (CI) strains. DISCUSSION: This present study highlights for reconstructing of evolutionary history, addressing host adaptation-related evolution and exploring the origin and divergence of CI genes in each Wolbachia supergroup. Our results thus not only provide a basis for further exploring the evolutionary history of Wolbachia adaptation under host selection but also reveal a new research direction for studying the molecular regulation of Wolbachia- induced cytoplasmic incompatibility.
Biological comparative study between Wolbachia-infected Aedes aegypti mosquito and Wolbachia-uninfected strain, Jeddah city, Saudi Arabia
24804A. G. Algamdi, F. M. Shaher and J. A. Mahyoub, Saudi J Biol Sci, 30:103581. 2023-02-02 08:32:08.
In this study, samples of Wolbachia-infected Aedes aegypti mosquitoes were collected from Al-Safa district in Jeddah city, Saudi Arabia. The presence of Wolbachia bacteria in mosquitoes was confirmed by PCR technique and they were reared and propagated in the laboratory. Comparative studies were conducted between Wolbachia-infected A. Aegypti and the Wolbachia-uninfected laboratory strain in terms of their ability to withstand drought, resist two types of insecticides and the activities of pesticide detoxification enzymes. The Wolbachia-infected A. aegypti strain proved less able to withstand the drought period, as the egg-hatching rate of the Wolbachia-uninfected strain was greater than that of the Wolbachia-infected strain after one, two and three months of dry periods. Compared to the Wolbachia-uninfected strain, the Wolbachia-infected strain demonstrated a relatively greater resistance to tested pesticides, namely Baton 100EC and Fendure 25EC which may be attributed to the higher levels of the detoxification enzymes glutathione-S-transferase and catalase and the lower levels of esterase and acetylcholine esterase.
Impact of randomised wmel Wolbachia deployments on notified dengue cases and insecticide fogging for dengue control in Yogyakarta City
24619C. Indriani, S. K. Tanamas, U. Khasanah, M. R. Ansari, Rubangi, W. Tantowijoyo, R. A. Ahmad, S. M. Dufault, N. P. Jewell, A. Utarini, C. P. Simmons and K. L. Anders, Glob Health Action, 16:2166650. 2023-01-26 09:27:00.
BACKGROUND: Releases of Wolbachia (wMel)-infected Aedes aegypti mosquitoes significantly reduced the incidence of virologically confirmed dengue in a previous cluster randomised trial in Yogyakarta City, Indonesia. Following the trial, wMel releases were extended to the untreated control areas, to achieve city-wide coverage of Wolbachia. OBJECTIVE: In this predefined analysis, we evaluated the impact of the wMel deployments in Yogyakarta on dengue hemorrhagic fever (DHF) case notifications and on the frequency of perifocal insecticide spraying by public health teams. METHODS: Monthly counts of DHF cases notified to the Yogyakarta District Health Office between January 2006 and May 2022 were modelled as a function of time-varying local wMel treatment status (fully- and partially-treated vs untreated, and by quintile of wMel prevalence). The frequency of insecticide fogging in wMel-treated and untreated areas was analysed using negative binomial regression. RESULTS: Notified DHF incidence was 83% lower in fully treated vs untreated periods (IRR 0.17 [95% CI 0.14, 0.20]), and 78% lower in areas with 80-100% wMel prevalence compared to areas with 0-20% wMel (IRR 0.23 [0.17, 0.30]). A similar intervention effect was observed at 60-80% wMel prevalence as at 80-100% prevalence (76% vs 78% efficacy, respectively). Pre-intervention, insecticide fogging occurred at similar frequencies in areas later randomised to wMel-treated and untreated arms of the trial. After wMel deployment, fogging occurred significantly less frequently in treated areas (IRR 0.17 [0.10, 0.30]). CONCLUSIONS: Deployments of wMel-infected Aedes aegypti mosquitoes resulted in an 83% reduction in the application of perifocal insecticide spraying, consistent with lower dengue case notifications in wMel-treated areas. These results show that the Wolbachia intervention effect demonstrated previously in a cluster randomised trial was also measurable from routine surveillance data.
Complicated expansion trajectories of insertion sequences and potential association with horizontal transfer of Wolbachia DNA
24573Y. H. Miao, D. W. Huang and J. H. Xiao, Zoological Research, 44:273-275. 2023-01-22 08:41:24.
Insertion sequences (ISs) are the simplest structural transposable elements (TEs) in prokaryotes, consisting only of a transposase coding sequence and its bilateral short terminal inverted repeats. Due to their gradually streamlined genomic construction, TEs rarely exist in the genomes of obligate endosymbionts. However, TE content, especially ISs, is abundant in the genome of Wolbachia bacteria, obligate endosymbionts widespread in arthropods and nematodes. Although IS indels are reported to affect genome structure and gene function in Wolbachia, the distribution patterns, sources, and transfer trajectories of ISs remain poorly understood. Furthermore, whether IS transposition is associated with dynamic horizontal transfer of Wolbachia DNA is still unclear. Based on distribution patterns in supergroup A Wolbachia strains, ISs accounted for 11% of the genome of the Wolbachia strain wWpum, one of the highest IS genome coverages reported for Wolbachia to date. Three types of ISs showed rapid expansion in wWpum, possibly due to horizontal transfer from other Wolbachia strain supergroups or more distant prokaryotes. We also found the first evidence that ISs can carry flanking Wolbachia sequences for transposition, resulting in the horizontal transfer of Wolbachia DNA into the eukaryotic genome, thus implying a potential association between ISs and horizontal gene transfer from endosymbionts to eukaryotes.
Wolbachia Promotes Its Own Uptake by Host Cells
24576L. B. Nevalainen, E. M. Layton and I. L. G. Newton, Infection and Immunity, e0055722. 2023-01-17 08:49:38.
Wolbachia pipientis is an incredibly widespread bacterial symbiont of insects, present in an estimated 25 to 52% of species worldwide. Wolbachia is faithfully maternally transmitted both in a laboratory setting and in the wild. In an established infection, Wolbachia is primarily intracellular, residing within host-derived vacuoles that are associated with the endoplasmic reticulum. However, Wolbachia also frequently transfers between host species, requiring an extracellular stage to its life cycle. Indeed, Wolbachia has been moved between insect species for the precise goal of controlling populations. The use of Wolbachia in this application requires that we better understand how it initiates and establishes new infections. Here, we designed a novel method for live tracking Wolbachia cells during infection using a combination of stains and microscopy. We show that live Wolbachia cells are taken up by host cells at a much faster rate than dead Wolbachia cells, indicating that Wolbachia bacteria play a role in their own uptake and that Wolbachia colonization is not just a passive process. We also show that the host actin cytoskeleton must be intact for this to occur and that drugs that disrupt the actin cytoskeleton effectively abrogate Wolbachia uptake. The development of this live infection assay will assist in future efforts to characterize Wolbachia factors used during host infection.
Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti
24468M. Hussain, G. Zhang, M. Leitner, L. M. Hedges and S. Asgari, iScience, 26:105836. 2023-01-15 08:41:00.
The endosymbiotic bacterium Wolbachia pipientis blocks replication of several arboviruses in transinfected Aedes aegypti mosquitoes. However, the mechanism of virus blocking remains poorly understood. Here, we characterized an RNase HI gene from Wolbachia, which is rapidly induced in response to dengue virus (DENV) infection. Knocking down w RNase HI using antisense RNA in Wolbachia-transinfected mosquito cell lines and A. aegypti mosquitoes led to increased DENV replication. Furthermore, overexpression of wRNase HI, in the absence of Wolbachia, led to reduced replication of a positive sense RNA virus, but had no effect on a negative sense RNA virus, a familiar scenario in Wolbachia-infected cells. Altogether, our results provide compelling evidence for the missing link between early Wolbachia-mediated virus blocking and degradation of viral RNA. These findings and the successful pioneered knockdown of Wolbachia genes using antisense RNA in cell line and mosquitoes enable new ways to manipulate and study the complex endosymbiont-host interactions.
Dynamics of an impulsive reaction-diffusion mosquitoes model with multiple control measures
24571Y. Li, H. Zhao and K. Wang, Mathematical Biosciences and Engineering, 20:775-806. 2023-01-14 08:34:08.
It is well-known that mosquito control is one of the effective methods to reduce and prevent the transmission of mosquito-borne diseases. In this paper, we formulate a reaction-diffusion impulsive hybrid model incorporating Wolbachia, impulsively spraying of insecticides, spatial heterogeneity, and seasonality to investigate the control of mosquito population. The sufficient conditions for mosquito extinction or successful Wolbachia persistence in a population of natural mosquitoes are derived. More importantly, we give the estimations of the spraying times of insecticides during a period for achieving the mosquito extinction and population replacement in a special case. A global attractivity of the positive periodic solution is analyzed under appropriate conditions. Numerical simulations disclose that spatial heterogeneity and seasonality have significant impacts on the design of mosquitoes control strategies. It is suggested to combine biological control and chemical pulse control under certain situations to reduce the natural mosquitoes. Further, our results reveal that the establishment of a higher level of population replacement depends on the strain type of the Wolbachia and the high initial occupancy of the Wolbachia-infected mosquitoes.
Single-cell transcriptome sequencing reveals Wolbachia-mediated modification in early stages of Drosophila spermatogenesis
24466W. Dou, B. Sun, Y. Miao, D. Huang and J. Xiao, Proceedings of the Royal Society B: Biological Sciences, 290:20221963. 2023-01-11 08:36:44.
Wolbachia are the most widely distributed intracellular bacteria, and their most common effect on host phenotype is cytoplasmic incompatibility (CI). A variety of models have been proposed to decipher the molecular mechanism of CI, among which the host modification (HM) model predicts that Wolbachia effectors play an important role in sperm modification. However, owing to the complexity of spermatogenesis and testicular cell-type heterogeneity, whether Wolbachia have different effects on cells at different stages of spermatogenesis or whether these effects are linked with CI remains unknown. Therefore, we used single-cell RNA sequencing to analyse gene expression profiles in adult male Drosophila testes that were infected or uninfected by Wolbachia. We found that Wolbachia significantly affected the proportion of different types of germ cells and affected multiple metabolic pathways in germ cells. Most importantly, Wolbachia had the greatest impact on germline stem cells, resulting in dysregulated expression of genes related to DNA compaction, and Wolbachia infection also influenced the histone-to-protamine transition in the late stage of sperm development. These results support the HM model and suggest that future studies on Wolbachia-induced CI should focus on cells in the early stages of spermatogenesis.
Heterogeneous distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
24464S. Durand, B. Lheraud, I. Giraud, N. Bech, F. Grandjean, T. Rigaud, J. Peccoud and R. Cordaux, Biology Letters, 19:20220457. 2023-01-11 08:32:10.
In the isopod Armadillidium vulgare, many females produce progenies with female-biased sex ratios, owing to two feminizing sex ratio distorters (SRD): Wolbachia endosymbionts and the f element. We investigated the distribution and population dynamics of these SRD and mitochondrial DNA variation in 16 populations from Europe and Japan. Confirming and extending results from the 1990s, we found that the SRD are present at variable frequencies in populations and that the f element is overall more frequent than Wolbachia. The two SRD never co-occur at high frequency in any population, suggesting an apparent mutual exclusion. We also detected Wolbachia or the f element in some males, which probably reflects insufficient titer to induce feminization or presence of masculinizing alleles. Our results are consistent with a single integration event of a Wolbachia genome in the A. vulgare genome at the origin of the f element, which contradicts an earlier hypothesis of frequent losses and gains. We identified strong linkage between Wolbachia strains and mitochondrial haplotypes, but no association between the f element and mitochondrial background. Our results open new perspectives on SRD evolutionary dynamics in A. vulgare, the evolution of genetic conflicts and their impact on the variability of sex determination systems.
Wolbachia endosymbionts manipulate GSC self-renewal and differentiation to enhance host fertility
24270S. L. Russell, J. R. Castillo and W. T. Sullivan, bioRxiv, 2022.12.15.520626. 2022-12-17 14:03:40.
The alphaproteobacterium Wolbachia pipientis infects thousands of arthropod and nematode species worldwide, making it a key target for host biological control. Wolbachia-driven host reproductive manipulations, such as cytoplasmic incompatibility (CI), are often credited for catapulting these intracellular bacteria to high frequencies in their host populations. Positive, perhaps mutualistic, reproductive manipulations may also increase infection frequencies, but they are not well understood on molecular, cellular, or organismal levels. Previous studies demonstrated that Wolbachia is capable of partially rescuing sex-lethal, a gene required for germline stem cell (GSC) self renewal and bag-of-marbles, a gene required for GSC differentiation. Here, we identify molecular and cellular mechanisms by which Wolbachia is able to influence molecularly distinct processes of GSC self renewal and differentiation through our discovery that the wMel strain rescues meiotic-P26 mutants. Mei-P26 is an essential translational regulator and is required for both GSC self-renewal and differentiation. We demonstrate that wMel rescues the fertility of flies lacking adequate mei-P26 dosage and function, and is sufficient to sustain infertile homozygous mei-P26 hypomorphic stocks indefinitely. Cytology revealed that wMel infection mitigates the impact of mei-P26 loss on both germline stem cell maintenance and cyst differentiation through restoring proper pMad, Bam, Sxl, and Orb expression. Rescue in males, amplification of dominant negative effects, and multiallelic rescue suggest that wMel either directly or indirectly replaces Mei-P26 function. Even in wild-type individuals, wMel infection elevates lifetime egg lay and hatch rates. Over time, the beneficial fertility reinforcement mechanisms described here may promote the emergence of mutualism and the breakdown of CI.HighlightsThe wMel strain of Wolbachia restores fertility in females and males deficient for the essential translational regulator meiotic-P26Mei-P26’s germline maintenance and oocyte cyst differentiation functions are genetically rescued by wMel infectionPerturbed pMad, Sxl, Bam, and Orb expression are mitigated by wMel infectionwMel infection elevates lifetime egg lay and hatch rates in wild-type fliesCompeting Interest StatementThe authors have declared no competing interest.
Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial
24268J. Ong, S. H. Ho, S. X. H. Soh, Y. Wong, Y. Ng, K. Vasquez, Y. L. Lai, Y. X. Setoh, C. S. Chong, V. Lee, J. C. C. Wong, C. H. Tan, S. Sim, L. C. Ng and J. T. Lim, Trials, 23:1023. 2022-12-17 13:57:59.
The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km(2), covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints:
Cell-based analysis reveals that sex-determining gene signals in Ostrinia are pivotally changed by male-killing Wolbachia
24288B. Herran, T. N. Sugimoto, K. Watanabe, S. Imanishi, T. Tsuchida, T. Matsuo, Y. Ishikawa and D. Kageyama, PNAS Nexus, pgac293. 2022-12-13 08:59:49.
Wolbachia, a maternally transmitted bacterium, shows male-killing, an adaptive phenotype for cytoplasmic elements, in various arthropod species during the early developmental stages. In lepidopteran insects, lethality of males is accounted for by improper dosage compensation in sex-linked genes owing to Wolbachia-induced feminization. Herein, we established Ostrinia scapulalis cell lines that retained sex specificity per the splicing pattern of the sex-determining gene doublesex (Osdsx). We found that Wolbachia transinfection in male cell lines enhanced the female-specific splice variant of Osdsx (OsdsxF) while suppressing the male-specific variant (OsdsxM), indicating that Wolbachia affects sex-determining gene signals even in vitro. Comparative transcriptome analysis isolated only two genes that behave differently upon Wolbachia infection. The two genes were respectively homologous to Masculinizer (BmMasc) and zinc finger-2 (Bmznf-2), male-specifically expressed sex-determining genes of the silkworm Bombyx mori that encode CCCH-type zinc finger motif proteins. By using cultured cells and organismal samples, OsMasc and Osznf-2 were found to be sex-determining genes of O. scapulalis that are subjected to sex-specific alternative splicing depending upon the chromosomal sex, developmental stage, and infection status. Overall, our findings expound the cellular autonomy in insect sex determination and the mechanism through which sex is manipulated by intracellular selfish microbes.
A Wolbachia factor for male killing in lepidopteran insects
24016S. Katsuma, K. Hirota, N. Matsuda-Imai, T. Fukui, T. Muro, K. Nishino, H. Kosako, K. Shoji, H. Takanashi, T. Fujii, S.-i. Arimura and T. Kiuchi, Nature Communications, 13:6764. 2022-11-14 12:59:35.
Bacterial symbionts, such as Wolbachia species, can manipulate the sexual development and reproduction of their insect hosts. For example, Wolbachia infection induces male-specific death in the Asian corn borer Ostrinia furnacalis by targeting the host factor Masculinizer (Masc), an essential protein for masculinization and dosage compensation in lepidopteran insects. Here we identify a Wolbachia protein, designated Oscar, which interacts with Masc via its ankyrin repeats. Embryonic expression of Oscar inhibits Masc-induced masculinization and leads to male killing in two lepidopteran insects, O. furnacalis and the silkworm Bombyx mori. Our study identifies a mechanism by which Wolbachia induce male killing of host progeny.
Independent evaluation of Wolbachia infected male mosquito releases for control of Aedes aegypti in Harris County, Texas, using a Bayesian abundance estimator
23969S. Lozano, K. Pritts, D. Duguma, C. Fredregill and R. Connelly, PLOS Neglected Tropical Diseases, 16:e0010907. 2022-11-14 12:37:36.
Among disease vectors, Aedes aegypti (L.) (Diptera: Culicidae) is one of the most insidious species in the world. The disease burden created by this species has dramatically increased in the past 50 years, and during this time countries have relied on pesticides for control and prevention of viruses borne by Ae. aegypti. The small number of available insecticides with different modes of action had led to increases in insecticide resistance, thus, strategies, like the “Incompatible Insect Technique” using Wolbachia’s cytoplasmic incompatibility are desirable. We evaluated the effect of releases of Wolbachia infected Ae. aegypti males on populations of wild Ae. aegypti in the metropolitan area of Houston, TX. Releases were conducted by the company MosquitoMate, Inc. To estimate mosquito population reduction, we used a mosquito abundance Bayesian hierarchical estimator that accounted for inefficient trapping. MosquitoMate previously reported a reduction of 78% for an intervention conducted in Miami, FL. In this experiment we found a reduction of 93% with 95% credibility intervals of 86% and 96% after six weeks of continual releases. A similar result was reported by Verily Life Sciences, 96% [94%, 97%], in releases made in Fresno, CA.
Influence of public hesitancy and receptivity on reactive behaviours towards releases of male Wolbachia-Aedes mosquitoes for dengue control
23860M. O. Lwin, Z. Ong, C. Panchapakesan, A. Sheldenkar, L. T. Soh, I. Chen, X. Li, W. Niah, K. Vasquez, S. Sim and L.-C. Ng, PLOS Neglected Tropical Diseases, 16:e0010910. 2022-11-11 10:06:20.
Singapore, a highly urbanized Asian tropical country that experiences periodic dengue outbreaks, is piloting field releases of male Wolbachia-carrying Aedes aegyptimosquitoes with the aim of suppressing urban populations of the primary dengue vector Aedes aegypti. This study proposes and assesses a model to explain the roles of hesitancy and receptivity towards Project Wolbachia–Singapore in influencing reactive mosquito prevention behaviors (reactive behaviors) towards the release of Wolbachia-Aedes mosquitoes for residents living in the release sites. Interestingly, both hesitancy and receptivity predicted greater instances of reactive behaviors. The model also examines the roles of general knowledge about Wolbachia technology, perceived severity of mosquito bites, perceived density of mosquitoes, and social responsibility as predictors of hesitancy, receptivity, and reactive behaviors towards the release of Wolbachia-Aedes mosquitoes. Hesitancy towards the project mediated the effects of general knowledge, perceived severity of mosquito bites, and perceived density of mosquitoes on reactive behaviors towards the releases, although receptivity towards the project did not. Having less knowledge about Project Wolbachia–Singapore was associated with higher hesitancy towards the project and higher likelihood of performing reactive behaviors towards the releases. Individuals who perceive mosquito bites to be more severe and think that there are more mosquitoes in their living environments were also more likely to be hesitant about the project and practice reactive behaviors. However, both hesitancy and receptivity towards the project mediated the effect of social responsibility on reactive behaviors. Receptivity towards the project was driven by social responsibility, which was also associated with reduced hesitancy towards the project. Our findings suggest that, to address the hesitancy reported by a minority of participants, future outreach efforts should focus on strengthening the public’s sense of social responsibility
Wolbachia inhibits ovarian formation and increases blood feeding rate in female Aedes aegypti
23858M.-J. Lau, P. A. Ross, N. M. Endersby-Harshman, Q. Yang and A. A. Hoffmann, PLOS Neglected Tropical Diseases, 16:e0010913. 2022-11-11 09:59:48.
Author summary Wolbachia bacteria reduce the transmission of dengue and other arboviruses transmitted by their mosquito hosts once they have invaded host populations. This invasion process is being undertaken in Aedes aegypti mosquito populations throughout the world but can be slowed by deleterious fitness costs that the Wolbachia bacteria have on their mosquito hosts. Here we investigate in detail a recently identified cost where one of the Wolbachia strains being used in invasions causes infertility in females when the females develop from eggs that have been stored for a period. We show that slowed larval development (through food reduction) can cause the same phenomenon and that the emerged females lack functional ovaries. These infertile females also take blood meals more often. The results have implications for the successful invasion of Wolbachia under ecological circumstances where the mosquito eggs have to persist in the absence of water for a period and where larval food is limiting.
Monotonicity properties arising in a simple model of Wolbachia invasion for wild mosquito populations
24568D. Vicencio, O. Vasilieva and P. Gajardo, Mathematical Biosciences and Engineering, 20:1148-1175. 2022-10-25 08:23:57.
Using tools borrowed from monotone dynamical system theory, in the proposed model, we prove the existence of an invariant threshold manifold that allows us to provide practical recommendations for performing single and periodic releases of Wolbachia-carrying mosquitoes, seeking the eventual elimination of wild insects that are capable of transmitting infections to humans. We illustrate these findings with numerical simulations using parameter values corresponding to the wMelPop strain of Wolbachia that is considered the best virus blocker but induces fitness loss in its carriers. In these tests, we considered multiple scenarios contrasting a periodic release strategy against a strategy with a single inundative release, comparing their effectiveness. Our study is presented as an expository and mathematically accessible tool to study the use of Wolbachia-based biocontrol versus more complex models.
Hidden endosymbionts: A male-killer concealed by another endosymbiont and a nuclear suppressor
23793K. M. Richardson, P. A. Ross, B. S. Cooper, W. R. Conner, T. Schmidt and A. A. Hoffmann, bioRxiv, 2022.10.19.512817. 2022-10-22 06:41:08.
Maternally transmitted endosymbiotic bacteria that cause male killing (MK) have only been described from a few insects, but this may reflect challenges in their detection rather than a rarity of MK. Here we identify MK Wolbachia in populations of Drosophila pseudotakahashii, present at a low frequency (around 4%) in natural populations and previously undetected due to a different fixed Wolbachia strain in this species expressing a different reproductive manipulation, cytoplasmic incompatibility (CI). The MK phenotype was eliminated after tetracycline treatment that removed Wolbachia. Molecular analyses indicated the MK phenotype to be expressed when a second Wolbachia strain was present alongside the CI Wolbachia. A genomic analysis highlighted Wolbachia regions diverged between the strains involving 17 genes and also identified the Wolbachia as representing an outgroup to a clade of Wolbachia infecting melanogaster-group species, including wRi-like and wMel-like strains. Doubly infected males induced CI with uninfected females but not females singly infected with CI-causing Wolbachia. The MK phenotype manifested at the larval stage and was transmitted maternally at a high fidelity but with occasional loss of the MK Wolbachia strain. A rapidly spreading dominant nuclear suppressor genetic element affecting MK was identified through backcrossing and subsequent analysis with ddRAD SNPs of the D. pseudotakahashii genome. These findings highlight the complexity of nuclear and microbial components affecting MK endosymbiont detection and dynamics in populations, and the challenges of making connections between endosymbionts and the host phenotypes affected by them.Competing Interest StatementThe authors have declared no competing interest.
GeneConvene Global Collaborative Webinar Series | Wolbachia Biology, Mechanisms and Applications 2022
23723David O'Brochta, GeneConvene Global Collaborative, 2022-10-15 06:57:26.
Intracellular and extracellular symbiotic/commensal bacteria have enormous potential when manipulated and deployed appropriately to serve as agents of control of insects and the pathogens they transmit. Wolbachia, an intracellular bacteria, is a well studied system and one that is used increasingly to control insect populations via cytoplasmic incompatibility and to alter the vectoral capacity of insect via pathogen inhibition. This webinar series will survey the applications of Wolbachia as a mosquito/dengue control intervention and the underlying biology that conditions its effectiveness.
Wolbachia wAlbB inhibit dengue and Zika infection in the mosquito Aedes aegypti with an Australian background
23714L. E. Hugo, G. Rašić, A. J. Maynard, L. Ambrose, C. Liddington, C. J. E. Thomas, N. S. Nath, M. Graham, C. Winterford, B. M. C. R. Wimalasiri-Yapa, Z. Xi, N. W. Beebe and G. J. Devine, PLOS Neglected Tropical Diseases, 16:e0010786. 2022-10-13 06:27:20.
Biological control of mosquito vectors using the endosymbiotic bacteria Wolbachia is an emerging strategy for the management of human arboviral diseases. We recently described the development of a strain of Aedes aegypti infected with the Wolbachia strain wAlbB (referred to as the wAlbB2-F4 strain) through simple backcrossing of wild type Australian mosquitoes with a wAlbB infected Ae. aegypti strain from the USA. Field releases of male wAlbB2-F4 mosquitoes resulted in the successful suppression of wild populations of mosquitoes in the trial sites by exploiting the strain’s Wolbachia-induced cytoplasmic incompatibility. We now demonstrate that the strain is resistant to infection by dengue and Zika viruses and is genetically similar to endemic Queensland populations. There was a fourfold reduction in the proportion of wAlbB2-F4 mosquitoes that became infected following a blood meal containing dengue 2 virus (16.7%) compared to wild type mosquitoes (69.2%) and a 6–7 fold reduction in the proportion of wAlbB2-F4 mosquitoes producing virus in saliva following a blood meal containing an epidemic strain of Zika virus (8.7% in comparison to 58.3% in wild type mosquitoes). Restriction-site Associated DNA (RAD) sequencing revealed that wAlbB2-F4 mosquitoes have > 98% Australian ancestry, confirming the successful introduction of the wAlbB2 infection into the Australian genomic background through backcrossing. Genotypic and phenotypic analyses showed the wAlbB2-F4 strain retains the insecticide susceptible phenotype and genotype of native Australian mosquitoes. We demonstrate that the Wolbachia wAlbB2-F4, in addition to being suitable for population suppression programs, can also be effective in population replacement programs given its inhibition of virus infection in mosquitoes. The ease at which a target mosquito population can be transfected with wAlbB2, while retaining the genotypes and phenotypes of the target population, shows the utility of this strain for controlling the Ae. aegypti mosquitoes and the pathogens they transmit.
Risk Assessment on the Release of Wolbachia-Infected Aedes aegypti in Yogyakarta, Indonesia
23707D. Buchori, A. Mawan, I. Nurhayati, A. Aryati, H. Kusnanto and U. K. Hadi, Insects, 13. 2022-10-12 08:16:52.
Wolbachia-infected Aedes aegypti is the latest technology that was developed to eliminate dengue fever. The Ministry of Research and Technology of the Republic of Indonesia (Kemenristekdikti) established an expert group to identify future potential risks that may occur over a period of 30 years associated with the release of Wolbachia-infected Ae. aegypti. The risk assessment consisted of identifying different hazards that may have impacts on humans and the environment. From the consensus among the experts, there were 56 hazards identified and categorized into 4 components, namely, ecological matters, efficacy in mosquito management, economic and sociocultural issues, and public health standards. There were 19 hazards in the ecological group. The overall likelihood in the ecology of the mosquito is very low (0.05), with moderate consequence (0.74), which resulted in negligible risk. For the efficacy in mosquito management group, there were 12 hazards that resulted in very low likelihood (0.11) with high consequence (0.85). The overall risk for mosquito management efficacy was very low (0.09). There were 14 hazards identified in the public health standard with very low likelihood (0.07), moderate consequence (0.50) and negligible risk (0.04). Lastly, 13 hazards were identified in the economic and sociocultural group with low likelihood (0.01) but of moderate consequence (0.5), which resulted in a very low risk (0.09). The risk severity level of the four components leading to the endpoint risk of “cause more harm” due to releasing Wolbachia-infected Ae. aegypti is negligible (0.01).
Wolbachia-Virus interactions and arbovirus control through population replacement in mosquitoes
23675T. H. Ant, M. V. Mancini, C. J. McNamara, S. M. Rainey and S. P. Sinkins, Pathogens and Global Health, 2022-10-07 08:27:10.
Following transfer into the primary arbovirus vector Aedes aegypti, several strains of the intracellular bacterium Wolbachia have been shown to inhibit the transmission of dengue, Zika, and chikungunya viruses, important human pathogens that cause significant morbidity and mortality worldwide. In addition to pathogen inhibition, many Wolbachia strains manipulate host reproduction, resulting in an invasive capacity of the bacterium in insect populations. This has led to the deployment of Wolbachia as a dengue control tool, and trials have reported significant reductions in transmission in release areas. Here, we discuss the possible mechanisms of Wolbachia-virus inhibition and the implications for long-term success of dengue control. We also consider the evidence presented in several reports that Wolbachia may cause an enhancement of replication of certain viruses under particular conditions, and conclude that these should not cause any concerns with respect to the application of Wolbachia to arbovirus control.
Fitness costs of Wolbachia shift in locally-adapted Aedes aegypti mosquitoes
23703P. A. Ross and A. A. Hoffmann, Environmental Microbiology, 2022-10-06 08:10:07.
Aedes aegypti mosquito eggs can remain quiescent for many months before hatching, allowing populations to persist through unfavorable conditions. Aedes aegypti infected with the Wolbachia strain wMel have been released in tropical and subtropical regions for dengue control. wMel reduces the viability of quiescent eggs, but this physiological cost might be expected to evolve in natural mosquito populations that frequently experience stressful conditions. We found that the cost of wMel infection differed consistently between mosquitoes collected from different locations and became weaker across laboratory generations, suggesting environment-specific adaptation of mosquitoes to the wMel infection. Reciprocal crossing experiments show that differences in the cost of wMel to quiescent egg viability were mainly due to mosquito genetic background and not Wolbachia origin. wMel-infected mosquitoes hatching from long-term quiescent eggs showed partial loss of cytoplasmic incompatibility and female infertility, highlighting additional costs of long-term quiescence. Our study provides the first evidence for a shift in Wolbachia phenotypic effects following deliberate field release and establishment and it highlights interactions between Wolbachia infections and mosquito genetic backgrounds. The unexpected changes in fitness costs observed here suggest potential tradeoffs with undescribed fitness benefits of the wMel infection.
Distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
236442022-09-30 08:15:09.
Externalities modulate the effectiveness of the Wolbachia release programme
23611E. E. Ooi and A. Wilder-Smith, The Lancet Infectious Diseases, 2022-09-28 09:16:47.
Despite the remarkable outcome in Yogyakarta, the wMel approach also has some challenges. In particular, the extent to which ecological, weather, and other external factors influence the dissemination and establishment of wMel in complex urban environments remains unclear. Whether the high and sustained penetration rate of wMel and the efficacy in preventing dengue that was observed in Yogyakarta are readily reproducible in other regions of the world that are vulnerable to repeated outbreaks of such viral diseases is also unclear. We therefore welcome the study into the real-world effectiveness of large-scale wMel release in the urban setting of Rio de Janeiro.3 The study assessed the rate of wMel introgression at the neighbourhood level and its effect on the localised incidence of dengue and chikungunya. Mosquitoes were released over a 2·5-year period starting in August, 2017.
Estimating the effect of the wMel release programme on the incidence of dengue and chikungunya in Rio de Janeiro, Brazil: a spatiotemporal modelling study
23608G. Ribeiro dos Santos, B. Durovni, V. Saraceni, T. I. Souza Riback, S. B. Pinto, K. L. Anders, et al., The Lancet Infectious Diseases, 2022-09-28 09:07:02.
Summary Background Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city. Methods 67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019. Findings On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32–44) reduction in the incidence of dengue and a 10% (4–16) reduction in the incidence of chikungunya. Interpretation Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes. Funding Bill & Melinda Gates Foundation and the European Research Council.
The Involvement of Atlastin in Dengue Virus and Wolbachia Infection in Aedes aegypti and Its Regulation by aae-miR-989
23637M. Hussain, T. Bradshaw, M. Lee and S. Asgari, Microbiology Spectrum, 2022-09-27 06:48:46.
Endoplasmic reticulum (ER)-shaping atlastin proteins (ATLs) have been demonstrated to play a functional role during flavivirus replication in mammalian cells. For dengue virus (DENV), atlastin is required in the formation of the replication organelles and RNA replication, virion assembly, production of the infectious virus particles, and trafficking or directing the association of vesicle packets with furin. Here, we investigated the involvement of atlastin in DENV replication in the mosquito Aedes aegypti and explored the possibility of its manipulation by the endosymbiotic bacterium Wolbachia to interfere with DENV replication. Results showed the expression of Ae. aegypti atlastin gene (AaATL) was upregulated in DENV-infected Aag2 cells, and its silencing led to reduced DENV replication. Contrary to our assumption that AaATL could be downregulated by Wolbachia, we did not find evidence for that in Wolbachia-infected cell lines, but this was the case in mosquitoes. Further, silencing AaATL did not have any effect on Wolbachia density. Our results also suggest that aae-miR-989 miRNA negatively regulates AaATL. The oversupply of the miRNA mimic led to reduced DENV replication consistent with the positive role of AaATL in DENV replication. Overall, the results favor AaATL’s involvement in DENV replication; however, there is no support that the protein is involved in Wolbachia-mediated DENV inhibition. In addition, the results contribute to discerning further possible overlapping functions of ATLs in mosquitoes and mammalian cells.
Wolbachia action in the sperm produces developmentally deferred chromosome segregation defects during the Drosophila mid-blastula transition
23615B. Warecki, S. W. A. Titen, M. S. Alam, G. Vega, N. Lemseffer, K. Hug, et al., eLife, 11:e81292. 2022-09-23 09:36:01.
Wolbachia, a vertically transmitted endosymbiont infecting many insects, spreads rapidly through uninfected populations by a mechanism known as cytoplasmic incompatibility (CI). In CI, a paternally delivered modification of the sperm leads to chromatin defects and lethality during and after the first mitosis of embryonic development in multiple species. However, whether CI-induced defects in later stage embryos are a consequence of the first division errors or caused by independent defects remains unresolved. To address this question, we focused on ~1/3 of embryos from CI crosses in Drosophila simulans that develop apparently normally through the first and subsequent pre-blastoderm divisions before exhibiting mitotic errors during the mid-blastula transition and gastrulation. We performed single embryo PCR and whole genome sequencing to find a large percentage of these developed CI-derived embryos bypass the first division defect. Using fluorescence in situ hybridization, we find increased chromosome segregation errors in gastrulating CI-derived embryos that had avoided the first division defect. Thus, Wolbachia action in the sperm induces developmentally deferred defects that are not a consequence of the first division errors. Like the immediate defect, the delayed defect is rescued through crosses to infected females. These studies inform current models on the molecular and cellular basis of CI.
Wolbachia strain wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking
23646X. Liang, C. H. Tan, Q. Sun, M. Zhang, P. J. Wong, M. I. Li, et al., PNAS Nexus, 2022-09-22 08:20:54.
The ability of the maternally transmitted endosymbiotic bacterium Wolbachia to induce cytoplasmic incompatibility (CI) and virus blocking makes it a promising weapon for combatting mosquito-borne diseases through either suppression or replacement of wild-type populations. Recent field trials show that both approaches significantly reduce the incidence of dengue fever in humans. However, new questions emerge about how Wolbachia-mosquito associations will co-evolve over time and whether Wolbachia-mediated virus blocking will be affected by the genetic diversity of mosquitoes and arboviruses in the real world. Here, we have compared the Wolbachia density and CI expression of two wAlbB-infected Aedes aegypti lines transinfected 15 years apart. We have also assessed wAlbB-mediated virus blocking against dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) viruses and examined whether host genetic backgrounds modulate viral blocking effects by comparing ZIKV infection in mosquitoes with a Mexican genetic background to those with a Singaporean background. Our results show that over 15 years, wAlbB maintained the capacity to form a stable association with Ae. aegypti in terms of both density and CI expression. There were variations in wAlbB-induced virus blocking against CHIKV, DENV, and ZIKV, and higher inhibitory effects on ZIKV in mosquitoes on the Singaporean genetic background than on the Mexican background. These results provide important information concerning the robustness and long-term stability of Wolbachia as a biocontrol agent for arbovirus disease control.
Genome sequencing and comparative analysis of Wolbachia strain wAlbA reveals Wolbachia-associated plasmids are common
23606J. Martinez, T. H. Ant, S. M. Murdochy, L. Tong, A. da Silva Filipe and S. P. Sinkins, PLOS Genetics, 18:e1010406. 2022-09-19 05:21:48.
Wolbachia is the most common bacterial symbiont of arthropods, being found in about half of terrestrial species around the globe. It is transmitted from mother to offspring, can spread rapidly by inducing various forms of reproductive parasitism and often provides protection against viral pathogens. These properties are being harnessed by disease control interventions introducing Wolbachia into wild populations of virus-transmitting mosquitoes. Here we sequenced the genome of wAlbA, a strain of the symbiont naturally found in Aedes albopictus mosquitoes and demonstrate that it is associated with two extrachromosomal plasmid elements. We then reanalysed publicly available sequencing data and found that plasmids are much more common in Wolbachia than previously thought. Some of them carry genes potentially important for symbiosis and reproductive manipulation as well as phage-like genes that may allow them to move between symbiont strains. Our findings provide a new framework for studying Wolbachia and will help the future development of genetic tools for manipulating symbiont genomes.
Bill Gates’ Colombian Mosquito Factory Breeding 30 Million Bacteria-Infected Mosquitos Per Week
23525anonymous, GREATGAMEINDIA, 2022-09-07 05:27:22.
Bill Gates’ Colombian ‘mosquito factory’ is breeding 30 million bacteria-infected mosquitos per week. The project’s objective appears to be to introduce Wolbachia into native mosquito populations by employing lab-bred mosquitoes, resulting in the infection of such populations. In a plant in Colombia, Bill Gates is currently producing 30 million bacterially-infected mosquitoes every week and he has threatened to “scale and deliver” the mosquitoes to “communities around the world.” As part of his World Mosquito Program (WMP), the Microsoft founder and self-declared World Health Czar has already invested $185 million in the establishment of the mosquito factory. What is the project’s stated purpose? In order to eradicate native mosquito populations thought to be responsible for dengue, zika, and other viral illnesses in humans, it is necessary to utilize mosquitoes that are infected with a bacteria that induces sterility.
Modified mosquito releases to fight dengue fever, chikungunya or yellow fever
23555Sewell, Tammy, OICANADIAN, 2022-09-05 14:35:46.
To date, only one technique based on genetically modified mosquitoes has been developed at an operational level, it is the RIDL technique (release of insects carrying a dominant lethal gene, or release of insects carrying a dominant lethality gene). Male mosquitoes which, unlike females, do not bite, are genetically modified. Their offspring die before reaching adulthood. This technique has received authorization from the US Environmental Protection Agency. Last spring, the private company Oxitec began a trial in Florida consisting in disseminating mosquito eggs Aedes aegypti (known to carry many viruses such as dengue fever, yellow fever, chikungunya and Zika) genetically modified in nature for three months.
An optimal control problem for dengue transmission model with Wolbachia and vaccination
23694J. Zhang, L. L. Liu, Y. Z. Li and Y. Wang, Communications In Nonlinear Science and Numerical Simulation, 116. 2022-09-02 07:47:59.
The release of Wolbachia-infected mosquitoes into the wild mosquitoes population is an excellent biological control strategy which can be effective against mosquito-borne infections. In this work, we propose a dengue transmission model that incorporates releasing Wolbachia into the wild mosquito population and vaccinating human population. We analyze the basic reproduction number, the existence and stability of the equilibria, and carry out the sensitivity analysis to quantify the effects of parameters on the basic reproduction number. The analysis shows that the basic reproduction number determines the stability of two equilibria, and two transmission probabilities are positively correlated with the basic reproduction number, especially, the transmission probability of human being infected byWolbachia-infected mosquitoes is more sensitive than that of wild mosquitoes. Based on an integrated control strategy for the prevention of dengue fever (vaccination, using mosquito nets, improved treatment of dengue and spraying insecticides), we derive the necessary conditions for the optimal control problem using Pontryagin's Maximum Principle and carry out numerical simulations by MATLAB. Finally, the cost-effectiveness analysis of several control strategies is examined to determine the most feasible strategy. It shows that the most cost-effective integrated strategy is vaccination, using mosquito nets and spraying insecticides. (c) 2022 Elsevier B.V. All rights reserved.
Bacterial supergroup-specific “cost” of Wolbachia infections in Nasonia vitripennis
23640A. Tiwary, R. Babu, R. Sen and R. Raychoudhury, Ecology and Evolution, 2022-09-01 08:00:24.
Abstract The maternally inherited endosymbiont, Wolbachia, is known to alter the reproductive biology of its arthropod hosts for its own benefit and can induce both positive and negative fitness effects in many hosts. Here, we describe the effects of the maintenance of two distinct Wolbachia infections, one each from supergroups A and B, on the parasitoid host Nasonia vitripennis. We compare the effect of Wolbachia infections on various traits between the uninfected, single A-infected, single B-infected, and double-infected lines with their cured versions. Contrary to some previous reports, our results suggest that there is a significant cost associated with the maintenance of Wolbachia infections where traits such as family size, fecundity, longevity, and rates of male copulation are compromised in Wolbachia-infected lines. The double Wolbachia infection has the most detrimental impact on the host as compared to single infections. Moreover, there is a supergroup-specific negative impact on these wasps as the supergroup B infection elicits the most pronounced negative effects. These negative effects can be attributed to a higher Wolbachia titer seen in the double and the single supergroup B infection lines when compared to supergroup A. Our findings raise important questions on the mechanism of survival and maintenance of these reproductive parasites in arthropod hosts.
Call for public consultation ̶ Development of Target Product Profiles (TPPs) for Wolbachia infected Aedes aegypti population replacement intervention
23511World Health Organization, WHO, 2022-08-31 19:42:27.
WHO aims to reduce the global burden of dengue by 25% by 2030. To reach this goal, it is imperative to provide control programmes with sustainable vector control tools. Wolbachia, a symbiotic bacterium that occurs naturally in many insects, has been successfully transferred into the Aedes aegypti mosquito and has been found to reduce the transmission of the dengue virus. Some studies have also shown that this intervention could be sustained for more extended periods. The WHO Vector Control Advisory Group has assessed this intervention and confirmed its public health value for dengue control. WHO has identified a need to develop the Target Product Profiles (TPPs) of current and emerging vector control products to support their optimization. Consequently, a Technical Advisory Group (TAG) was established by WHO to define optimal and minimally acceptable characteristics for developing the TPPs. The TAG is being supported by the WHO secretariat.
Comparative Ubiquitome Analysis Reveals Deubiquitinating Effects Induced by Wolbachia Infection in Drosophila melanogaster
23489Q. Zong, B. Mao, H. B. Zhang, B. Wang, W. J. Yu, Z. W. Wang and Y. F. Wang, International Journal Molecular Science, 23. 2022-08-21 07:14:27.
The endosymbiotic Wolbachia bacteria frequently cause cytoplasmic incompatibility (CI) in their insect hosts, where Wolbachia-infected males cross with uninfected females, leading to no or fewer progenies, indicating a paternal modification by Wolbachia. Recent studies have identified a Wolbachia protein, CidB, containing a DUB (deubiquitylating enzyme) domain, which can be loaded into host sperm nuclei and involved in CI, though the DUB activity is not necessary for CI in Drosophila melanogaster. To investigate whether and how Wolbachia affect protein ubiquitination in testes of male hosts and are thus involved in male fertility, we compared the protein and ubiquitinated protein expressions in D. melanogaster testes with and without Wolbachia. A total of 643 differentially expressed proteins (DEPs) and 309 differentially expressed ubiquitinated proteins (DEUPs) were identified to have at least a 1.5-fold change with a p-value of <0.05. Many DEPs were enriched in metabolic pathway, ribosome, RNA transport, and post-translational protein modification pathways. Many DEUPs were involved in metabolism, ribosome, and proteasome pathways. Notably, 98.1% DEUPs were downregulated in the presence of Wolbachia. Four genes coding for DEUPs in ubiquitin proteasome pathways were knocked down, respectively, in Wolbachia-free fly testes. Among them, Rpn6 and Rpn7 knockdown caused male sterility, with no mature sperm in seminal vesicles. These results reveal deubiquitylating effects induced by Wolbachia infection, suggesting that Wolbachia can widely deubiquitinate proteins that have crucial functions in male fertility of their hosts, but are not involved in CI. Our data provide new insights into the regulatory mechanisms of endosymbiont/host interactions and male fertility.
Effect of Wolbachia Infection and Adult Food on the Sexual Signaling of Males of the Mediterranean Fruit Fly Ceratitis capitata
23487G. A. Kyritsis, P. Koskinioti, K. Bourtzis and N. T. Papadopoulos, Insects, 13. 2022-08-17 07:10:32.
Sexual signaling is a fundamental component of sexual behavior of Ceratitis capitata that highly determines males' mating success. Nutritional status and age are dominant factors known to affect males' signaling performance and define the female decision to accept a male as a sexual partner. Wolbachia pipientis, a widespread endosymbiotic bacterium of insects and other arthropods, exerts several biological effects on its hosts. However, the effects of Wolbachia infection on the sexual behavior of medfly and the interaction between Wolbachia infection and adult food remain unexplored. This study was conducted to determine the effects of Wolbachia on sexual signaling of protein-fed and protein-deprived males. Our findings demonstrate that: (a) Wolbachia infection reduced male sexual signaling rates in both food regimes; (b) the negative effect of Wolbachia infection was more pronounced on protein-fed than protein-deprived males, and it was higher at younger ages, indicating that the bacterium regulates male sexual maturity; (c) Wolbachia infection alters the daily pattern of sexual signaling; and (d) protein deprivation bears significant descent on sexual signaling frequency of the uninfected males, whereas no difference was observed for the Wolbachia-infected males. The impact of our findings on the implementation of Incompatible Insect Technique (IIT) or the combined SIT/IIT towards controlling insect pests is discussed.
Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: a modeling study
23424J. Li and J. Champer, bioRxiv, 2022.08.09.503337. 2022-08-11 07:25:47.
By using both mathematical and simulation models, we found that a drive containing CifA and CifB together create a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence.
Changing mosquito genes, spreading bacteria: Science sees success vs dengue
23421C. E. Baclig, INQUIRER.NET, 2022-08-10 08:51:03.
Wolbachia, according to WMP, are extremely common bacteria that occur naturally in 50 percent of insect species, including mosquitoes, fruit flies, moths, dragonflies, and butterflies. Aedes aegypti or dengue-carrying mosquitoes, however, do not normally carry Wolbachia. Studies showed that the bacteria make it difficult for viruses, such as dengue, Zika, chikungunya, and yellow fever, to reproduce inside the Aedes aegypti mosquitoes—making the mosquitoes much less likely to spread viruses when they bite people. “This means that when Aedes aegypti mosquitoes carry natural Wolbachia bacteria, the transmission of viruses like dengue, Zika, chikungunya, and yellow fever is reduced,” the organization explained. The WMP breeds Wolbachia-carrying mosquitoes and releases them into areas hit by mosquito-borne diseases. This means there will be “less risk of disease in communities where Wolbachia is established in the local mosquito population.”
Studies on the fitness characteristics of wMel- and wAlbB-introgressed Aedes aegypti (Pud) lines in comparison with wMel- and wAlbB-transinfected Aedes aegypti (Aus) and wild-type Aedes aegypti (Pud) lines
23485C. Sadanandane, K. Gunasekaran, D. Panneer, S. K. Subbarao, M. Rahi, B. Vijayakumar, V. Athithan, A. Sakthivel, S. Dinesh and P. Jambulingam, Frontiers in Microbiology, 13:947857. 2022-08-05 07:02:55.
Wolbachia, an intracellular maternally transmitted endosymbiont, has been shown to interfere with the replication of dengue virus in Aedes aegypti mosquitoes. The Wolbachia-transinfected Ae. aegypti has been currently released in many countries to test its effectiveness in preventing the transmission of dengue virus. ICMR-Vector Control Research Centre in collaboration with World Mosquito Program Monash University, Australia, has generated two new Wolbachia-introgressed Ae. aegypti Puducherry (Pud) lines via backcrossing Ae. aegypti females of Australian (Aus) strains, infected with wMel and wAlbB Wolbachia with wild-type Ae. aegypti Puducherry (Pud) males. Wolbachia infections are known to induce a fitness cost and confer benefit on the host mosquito populations that will influence spread of the Wolbachia into native wild mosquito populations during the field release. Hence, the induced fitness cost or benefit/advantage in the two newly generated Ae. aegypti (Pud) lines was assessed in the laboratory in comparison with the wild-type Ae. aegypti (Pud) strain. In addition, maternal transmission (MT) efficiency, induced cytoplasmic incompatibility (CI), and insecticide resistance status of the two (Pud) lines were determined to assess the likely frequency of wMel and wAlbB infections in the native wild population after field invasion. The study shows that wMel and wAlbB infections did not induce any fitness cost on the two newly generated (Pud) lines. Rather, in terms of wing length, fecundity, egg hatch rate, and adult survival, the Wolbachia introgression conferred fitness benefits on the (Pud) lines compared to uninfected Wolbachia free wild Ae. aegypti population. wMel and wAlbB exhibited a high maternal transmission (99-100%) and induced nearly complete (98-100%) cytoplasmic incompatibility. Both the (Pud) lines were resistant to deltamethrin, malathion, DDT, and temephos, and the level of resistance was almost the same between the two lines as in the wild type. Overall, the stable association of wMel and wAlbB established with Ae. aegypti and the reproductive advantages of the (Pud) lines encourage a pilot release in the field for population replacement potential.
Wolbachia Dynamics in Mosquitoes with Incomplete CI and Imperfect Maternal Transmission by a DDE System
23393Y. Su, B. Zheng and X. Zou, Bulletin of Mathematical Biology, 84:95. 2022-08-01 08:09:11.
In this paper, we propose a delay differential equation model to describe the Wolbachia infection dynamics in mosquitoes in which the key factor of cytoplasmic incompactibility (CI) is incorporated in a more natural way than those in the literature. By analyzing the dynamics of the model, we are able to obtain some information on the impact of four important parameters: the competition capabilities of the wild mosquitoes and infected mosquitoes, the maternal transmission level and the CI level. The analytic results show that there are ranges of parameters that support competition exclusion principle, and there are also ranges of parameters that allow co-persistence for both wild and infected mosquitoes. These ranges account for the scenarios of failure of invasion, invasion and suppressing the wild mosquitoes, and invasion and replacing the wild mosquitoes. We also discuss some possible future problems both in mathematics and in modeling.
Wolbachia wPip Blocks Zika Virus Transovarial Transmission in Aedes albopictus
23333Y. Guo, J. Guo, Y. Li, X. Zheng and Y. Wu, Microbiol Spectrum, e0263321. 2022-07-27 08:36:55.
Area-wide application of Wolbachia to suppress mosquito populations and their transmitted viruses has achieved success in multiple countries. However, the mass release of Wolbachia-infected male mosquitoes involves a potential risk of accidentally releasing fertile females. In this study, we employed ovarian cells of the Ae. albopictus GUA, HC, and GT lines, which exhibit key traits, and compared them to better understand how Wolbachia inhibits ZIKV transovarial transmission. Our results showed an almost complete blockade of ZIKV transmission in HC female mosquitoes. Wolbachia in natively infected GUA mosquitoes negative affected ZIKV, and this interference was shown by slightly lower loads than those in HC mosquitoes. Overall, our work helps show how Wolbachia blocks ZIKV expansion and maintenance in the ovaries of Ae. albopictus and aids in understanding Wolbachia-ZIKV interactions in mosquitoes.
Developing Wolbachia-based disease interventions for an extreme environment
23309P. A. Ross, S. Elfekih, S. Collier, M. J. Klein, S. S. Lee, M. Dunn, S. Jackson, Y. Zhang, J. K. Axford, X. Gu, M. S. Nasar, P. N. Paradkar, E. A. Taoufik, F. M. Jiggins, A. M. Almalik, M. B. Al-Fageeh and A. A. Hoffmann, bioRxiv, 2022.07.26.501527. 2022-07-27 07:59:12.
Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced mosquito heat tolerance and egg viability, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.Competing Interest StatementThe authors have declared no competing interest.
Lack of robust evidence for a Wolbachia infection in Anopheles gambiae from Burkina Faso
23300S. P. Sawadogo, D. A. Kabore, E. B. Tibiri, A. Hughes, O. Gnankine, S. Quek, A. Diabaté, H. Ranson, G. L. Hughes and R. K. Dabiré, Medical and Veterinary Entomology, 2022-07-25 07:31:44.
The endosymbiont Wolbachia can have major effects on the reproductive fitness, and vectorial capacity of host insects and may provide new avenues to control mosquito-borne pathogens. Anopheles gambiae s.l is the major vector of malaria in Africa but the use of Wolbachia in this species has been limited by challenges in establishing stable transinfected lines and uncertainty around native infections. High frequencies of infection of Wolbachia have been previously reported in An. gambiae collected from the Valle du Kou region of Burkina Faso in 2011 and 2014. Here, we re-evaluated the occurrence of Wolbachia in natural samples, collected from Valle du Kou over a 12-year time span, and in addition, expanded sampling to other sites in Burkina Faso. Our results showed that, in contrast to earlier reports, Wolbachia is present at an extremely low prevalence in natural population of An. gambiae. From 5341 samples analysed, only 29 were positive for Wolbachia by nested PCR representing 0.54% of prevalence. No positive samples were found with regular PCR. Phylogenetic analysis of 16S rRNA gene amplicons clustered across supergroup B, with some having similarity to sequences previously found in Anopheles from Burkina Faso. However, we cannot discount the possibility that the amplicon positive samples we detected were due to environmental contamination or were false positives. Regardless, the lack of a prominent native infection in An. gambiae s.l. is encouraging for applications utilizing Wolbachia transinfected mosquitoes for malaria control.
Attempts to use breeding approaches in Aedes aegypti to create lines with distinct and stable relative Wolbachia densities
23279A. J. Mejia, L. Jimenez, H. L. C. Dutra, R. Perera and E. A. McGraw, Heredity, 2022-07-22 10:12:25.
Wolbachia is an insect endosymbiont being used for biological control in the mosquito Aedes aegypti because it causes cytoplasmic incompatibility (CI) and limits viral replication of dengue, chikungunya, and Zika viruses. While the genetic mechanism of pathogen blocking (PB) is not fully understood, the strength of both CI and PB are positively correlated with Wolbachia densities in the host. Wolbachia densities are determined by a combination of Wolbachia strain and insect genotype, as well as interactions with the environment. We employed both artificial selection and inbreeding with the goal of creating lines of Ae. aegypti with heritable and distinct Wolbachia densities so that we might better dissect the mechanism underlying PB. We were unable to shift the mean relative Wolbachia density in Ae. aegypti lines by either strategy, with relative densities instead tending to cycle over a narrow range. In lieu of this, we used Wolbachia densities in mosquito legs as predictors of relative densities in the remaining individual’s carcass. Because we worked with outbred mosquitoes, our findings indicate either a lack of genetic variation in the mosquito for controlling relative density, natural selection against extreme densities, or a predominance of environmental factors affecting densities. Our study reveals that there are moderating forces acting on relative Wolbachia densities that may help to stabilize density phenotypes post field release. We also show a means to accurately bin vector carcasses into high and low categories for non-DNA omics-based studies of Wolbachia-mediated traits.
cifB-transcript levels largely explain cytoplasmic incompatibility variation across divergent Wolbachia
23074J. D. Shropshire, E. Hamant, W. R. Conner and B. S. Cooper, PNAS Nexus, 2022-06-28 13:29:28.
Divergent hosts often associate with intracellular microbes that influence their fitness. Maternally transmitted Wolbachia bacteria are the most common of these endosymbionts due largely to cytoplasmic incompatibility (CI) that kills uninfected embryos fertilized by Wolbachia-infected males. Closely related infections in females rescue CI, providing a relative fitness advantage that drives Wolbachia to high frequencies. One prophage-associated gene (cifA) governs rescue and two contribute to CI (cifA and cifB), but CI strength ranges from very strong to very weak for unknown reasons. Here, we investigate CI-strength variation and its mechanistic underpinnings in a phylogenetic context across 20 million years (MY) of Wolbachia evolution in Drosophila hosts diverged up to 50 MY. These Wolbachia encode diverse Cif proteins (100–7.4% pairwise similarity), and AlphaFold structural analyses suggest that CifB sequence similarities do not predict structural similarities. We demonstrate that cifB-transcript levels in testes explain CI strength across all but two focal systems. Despite phylogenetic discordance among cifs and the bulk of the Wolbachia genome, closely related Wolbachia tend to cause similar CI strengths and transcribe cifB at similar levels. This indicates that other non-cif regions of the Wolbachia genome modulate cif-transcript levels. CI strength also increases with the length of the host's larval life stage, presumably due to prolonged cif action. Our findings reveal that cifB-transcript levels largely explain CI strength while highlighting other covariates. Elucidating CI's mechanism contributes to our understanding of Wolbachia spread in natural systems and the efficacy of CI-based biocontrol of arboviruses and agricultural pests globally.
Sensitivity of wMel and wAlbB Wolbachia infections in Aedes aegypti Puducherry (Indian) strains to heat stress during larval development
23056K. Gunasekaran, C. Sadanandane, D. Panneer, A. Kumar, M. Rahi, S. Dinesh, B. Vijayakumar, M. Krishnaraja, S. K. Subbarao and P. Jambulingam, Parasites and Vectors, 15:221. 2022-06-21 15:19:54.
BACKGROUND: ICMR-Vector Control Research Centre, Puducherry, India, developed two colonies of Aedes aegypti infected with wMel and wAlbB Wolbacia strains called Ae. aegypti (Pud) lines for dengue control. The sensitivity of wMel and wAlbB strains in Ae. aegypti (Pud) lines to heat stress was studied. METHODS: wMel and wAlbB infected and uninfected Ae. aegypti larvae (first to fourth instars) were reared in the laboratory to adults at 26 °C, 30 °C, 36 °C and 40 °C constant temperatures and also 26-30 °C, 26-36 °C and 26-40 °C diurnal cyclic temperatures. The adults were tested for Wolbachia infection. Experiments were also carried out rearing the larvae under simulated field conditions in summer (April and June) under sunlight using fully open and half open bowls and also under sunlight and natural shade. RESULTS: At 36 °C and 40 °C constant temperatures, complete larval mortality was observed. At 30 °C and 26 °C, no larval mortality occurred, but Wolbachia density was relatively low in wMel infected males compared to control (maintained at 26 ± 1 °C). At diurnal cyclic temperature of 26-40 °C, Wolbachia density was reduced in males of both the (Pud) lines, but not in females. At 26-36 °C, reduction in Wolbachia density was observed in wMel males but not in wAlbB males. At 26-30 °C, no significant reduction in Wolbachia density was observed with wMel and wAlbB strains. In simulated field conditions (April), under sunlight, the daytime water temperature reached a maximum of 35.7 °C in both full and half open bowls. No larval mortality occurred. Wolbachia frequency and density was reduced in wMel-infected Ae. aegypti (Pud) males from both type of bowls and in females from full open bowls, and in wAlbB males from half open bowls. In June, rearing of larvae under sunlight, the first-instar larvae experienced a maximum daytime water temperature of > 38 °C that caused complete mortality. No larval mortality was observed in bowls kept under shade (< 32 °C). CONCLUSIONS: Exposure of larvae to higher rearing temperatures in the laboratory and simulated-field conditions reduced the densities of wMel and wAlbB strains particularly in males, but the impact was more pronounced for wMel strain. The actual effect of heat stress on the stability of these two Wolbachia strains needs to be tested under natural field conditions.
Natural and Engineered Sex Ratio Distortion in Insects
23010A. Compton and Z. Tu, Frontiers in Ecology and Evolution, 10. 2022-06-15 08:25:52.
Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.
Male-killing-associated bacteriophage WO identified from comparisons of Wolbachia endosymbionts of Homona magnanima
22901H. Arai, H. Anbutsu, Y. Nishikawa, M. Kogawa, K. Ishii, M. Hosokawa, S.-R. Lin, M. Ueda, M. Nakai, Y. Kunimi, T. Harumoto, D. Kageyama, H. Takeyama and M. N. Inoue, bioRxiv, 2022-06-13 06:22:33.
The origin and mechanism of male-killing, an advantageous strategy employed by maternally transmitted symbionts such as Wolbachia, remain unclear. We compared genomes of four Wolbachia strains derived from Homona magnanima, a male-killing strain wHm-t (1.5 Mb), and three non-male-killing strains, wHm-a (1.1 Mb), wHm-b (1.3 Mb), and wHm-c (1.4 Mb). A wHm-t-specific 76-kbp prophage region harboured two tandemly arrayed WO-mediated killing (wmk) gene homologs (wmk-1/wmk-2 and wmk-3/wmk-4). Of these, wmk-1 or wmk-3 killed almost all Drosophila melanogaster individuals when transgenically overexpressed. Dual expression of wmk-3 and wmk-4 killed all males and rescued females. We propose a novel hypothesis wherein horizontally transmitted proto-Wolbachia with a single wmk killed both sexes, and tandem duplication of wmk allowed an evolutionary transition to a vertically transmitted symbiont, causing male-killing. Our study highlights the bacteriophage as a critical driver of the evolution of male-killing and argues for a conserved male-killing mechanism in diverse insects.Competing Interest StatementThe authors have declared no competing interest.
Mosquito control to save Hawaiian honeycreepers does not involve GMOs
22859Department of Land and Natural Resources, Hawaii Department of Land and Natural Resources, 2022-06-08 08:42:00.
Despite misinformation circulating on social media, the importation of “incompatible-male” mosquitoes to control populations of wild mosquitoes and to save four native bird species from extinction, does not involve the use of any genetically modified organisms (GMOs) or genetically engineered (GE) organisms. On Thursday, the Plant and Animal Advisory Committee of the Dept. of Agriculture will consider listing three species of mosquitoes on its Restricted Species List A. The listing would allow the importation of three species of mosquitoes, all of which are already present in Hawai‘i. One of these, the Southern House Mosquito (Culex quinquefasciatus) isresponsible for sharp declines in the populations of many honeycreeper species on Kaua‘i, Maui, and Hawai‘i Island. The other two species – Yellow Fever Mosquito (Aedes aegypti) and Asian Tiger Mosquito (Aedes albopictus) – transmit human diseases.
Establishment of Wolbachia infection in Aedes aegypti from Pakistan via embryonic microinjection and semi-field evaluation of general fitness of resultant mosquito population
22856M. S. Sarwar, N. Jahan, A. Ali, H. K. Yousaf and I. Munzoor, Parasites and Vectors, 15:191. 2022-06-06 08:36:19.
BACKGROUND: Dengue is a mosquito-borne viral disease that is mainly spread by Aedes aegypti. It is prevalent on five continents, predominantly in tropical and sub-tropical zones across the world. Wolbachia bacteria have been extensively used in vector control strategies worldwide. The focus of the current study was to obtain a natural population of Ae. aegypti harbouring Wolbachia and to determine the impact of this bacteria on the new host in a semi-field environment. METHODS: Wolbachia-infected Aedes albopictus was collected from the city of Lahore, Punjab, Pakistan, and Wolbachia were successfully introduced into laboratory-reared Ae. aegypti via embryonic microinjection. The stable vertical transmission of wAlbB in the host population was observed for eight generations, and the impact of Wolbachia on the general fitness of the host was evaluated in semi-field conditions. RESULTS: In the laboratory and semi-field experiments, wAlbB Wolbachia presented a strong cytoplasmic incompatibility (CI) effect, evidenced as zero egg hatching, in crosses between Wolbachia-infected males and wild (uninfected) females of Ae. aegypti. Wolbachia infection had no noticeable impact on the general fitness (P > 0.05), fecundity, body size (females and males) and mating competitiveness of the new host, Ae. aegypti. However, there was a significant decrease in female fertility (egg hatch) (P < 0.001). In addition, under starvation conditions, there was a remarkable decrease (P < 0.0001) in the life span of Wolbachia-infected females compared to uninfected females (4 vs. > 5 days, respectively). CONCLUSIONS: Wolbachia strain wAlbB has a great potential to control the dengue vector in Ae. aegypti populations by producing 100% CI with a limited burden on its host in natural field conditions. This strain can be used as a biological tool against vector-borne diseases.
Modifying mosquitoes to suppress disease transmission: Is the long wait over?
22854J. R. Powell, Genetics, 2022-06-02 08:31:17.
For more than 50 years it has been a dream of medical entomologists and public health workers to control diseases like malaria and dengue fever by modifying, through genetics and other methods, the arthropods that transmit them to humans. A brief synopsis of the history of these efforts as applied to mosquitoes is presented; none proved to be effective in reducing disease prevalence. Only in the last few years have novel approaches been developed or proposed that indicate the long wait may be over. Three recent developments are particularly promising: CRISPR-Cas9 driven genetic modification, shifting naturally occurring allele frequencies, and microbe-based modifications. The last is the furthest along in implementation. Dengue fever incidence has been reduced between 40% and 96% in 4 different regions of the world where Wolbachia-infected Aedes aegypti have been established in the field. It is not yet clear how sustainable such control programs will prove to be, but there is good reason for optimism. In light of this, the time is ripe for reinvigorated research on vectors, especially genetics. Vector-borne diseases primarily affect under-developed countries and thus have not received the attention they deserve from wealthier countries with well-developed and funded biomedical research establishments.
Wolbachia interacts with the microbiome to shape fitness-associated traits during seasonal adaptation in Drosophila melanogaster
22693L. P. Henry, M. Fernandez, S. Wolf and J. Ayroles, bioRxiv, 2022.05.31.494239. 2022-06-01 14:39:02.
The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the evolutionary effects of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal adaptation with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, interactions between Wolbachia and the microbiome contributed to fitness-associated traits. Wolbachia often exerted negative fitness effects on hosts, and the microbiome modulated these effects. Our work supports recent theoretical advances suggesting that hosts in temporally fluctuating environments benefit from flexible microbial associations with low transmission fidelity--specifically when changes in the microbiome can better enable host phenotypes to match environment change. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes and the utility of Wolbachia in combating vector-borne disease.Competing Interest StatementThe authors have declared no competing interest.
Reply to: Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes
22643J. E. Crawford, K. C. Hopkins, A. Buchman, T. Zha, P. Howell, E. Kakani, J. R. Ohm, N. Snoad, L. Upson, J. Holeman, P. Massaro, S. L. Dobson, F. S. Mulligan and B. J. White, Nature Biotechnology, 2022-05-26 06:34:15.
We appreciate the comments from Bouyer et al. under their mandate as a United Nations agency program (‘to promote the safe and appropriate use of nuclear techniques and related technologies in food and agriculture’) on our paper1 . The centuries-old fight against mosquito-borne disease has entered a new phase that is both exciting and fast-moving. Many promising technologies and techniques have been developed in the past 2 decades, including mosquito colonies stably infected with Wolbachia2 mosquitoes3,4, a CRISPR–Cas9-based gene drive5 nations of these techniques with older approaches (that is, irradiated Wolbachia releases6,7 , genetically modified sterile and even combi). In a world where more than half of all humans are at risk of contracting mosquito-borne diseases across a range of economic and geographic landscapes, we think that an array of tools will be needed to turn the tide against the massive public health burden of these diseases.
Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes
22641J. Bouyer, H. Maiga and M. J. B. Vreysen, Nature Biotechnology, 2022-05-26 06:27:58.
A paper by Crawford et al.1 titled ‘Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations’ reports a mosquito control suppression trial carried out from2017 to 2018 in Fresco Country, California, USA1 . Between 7.5 million and 14.4 million Wolbachia-infected male mosquitoes were released during the study, which achieved suppression rates of 69% and 95%, respectively. Although the work provided important insights for future Aedes genetic control programs—particularly the information on the immigration of fertile females into release areas—the paper contains several omissions and errors. Below, we discuss how these relate to three main areas: regulatory oversight, entomological efficiency and, finally, cost efficiency.
Perplexing dynamics of Wolbachia proteins for cytoplasmic incompatibility
22582T. Harumoto and T. Fukatsu, PLOS Biology, 20:e3001644. 2022-05-25 09:23:59.
The mechanism of symbiont-induced cytoplasmic incompatibility has been a long-lasting mystery. This Primer explores a new study on Wolbachia’s Cif proteins in PLOS Biology that provides supportive evidence for the “Host-Modification Model,” although the alternative “Toxin-Antidote Model” is still in the running.
The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility
22570R. Kaur, B. A. Leigh, I. T. Ritchie and S. R. Bordenstein, PLOS Biology, 20:e3001584. 2022-05-24 08:55:13.
In Drosophila melanogaster, germline expression of the Wolbachia proteins CifA and CifB causes cytoplasmic incompatibility, but how this impairs male reproduction remains unclear. This study shows how Cif proteins encoded by the endosymbiont prophage invade the fly’s gametic nuclei and modify the histone-protamine transition of spermatogenesis.
Wolbachia 16S rRNA haplotypes detected in wild Anopheles stephensi in eastern Ethiopia
22568E. Waymire, S. Duddu, S. Yared, D. Getachew, D. Dengela, S. R. Bordenstein, M. Balkew, S. Zohdy, S. R. Irish and T. E. Carter, Parasites and Vectors, 15:178. 2022-05-24 08:50:15.
About two out of three Ethiopians are at risk of malaria, a disease caused by the parasites Plasmodium falciparum and Plasmodium vivax. Anopheles stephensi, an invasive vector typically found in South Asia and the Middle East, was recently found to be distributed across eastern and central Ethiopia and is capable of transmitting both P. falciparum and P. vivax. The detection of this vector in the Horn of Africa (HOA) coupled with widespread insecticide resistance requires that new methods of vector control be investigated in order to control the spread of malaria. Wolbachia, a naturally occurring endosymbiotic bacterium of mosquitoes, has been identified as a potential vector control tool that can be explored for the control of malaria transmission. Wolbachia could be used to control the mosquito population through suppression or potentially decrease malaria transmission through population replacement. However, the presence of Wolbachia in wild An. stephensi in eastern Ethiopia is unknown. This study aimed to identify the presence and diversity of Wolbachia in An. stephensi across eastern Ethiopia.
Strategies to Mitigate Establishment under the Wolbachia Incompatible Insect Technique
23104S. Soh, S. H. Ho, J. Ong, A. Seah, B. S. Dickens, K. W. Tan, J. R. Koo, A. R. Cook, S. Sim, C. H. Tan, L. C. Ng and J. T. Lim, Viruses, 14. 2022-05-24 08:10:53.
The Incompatible Insect Technique (IIT) strategy involves the release of male mosquitoes infected with the bacterium Wolbachia. Regular releases of male Wolbachia-infected mosquitoes can lead to the suppression of mosquito populations, thereby reducing the risk of transmission of vector-borne diseases such as dengue. However, due to imperfect sex-sorting under IIT, fertile Wolbachia-infected female mosquitoes may potentially be unintentionally released into the environment, which may result in replacement and failure to suppress the mosquito populations. As such, mitigating Wolbachia establishment requires a combination of IIT with other strategies. We introduced a simple compartmental model to simulate ex-ante mosquito population dynamics subjected to a Wolbachia-IIT programme. In silico, we explored the risk of replacement, and strategies that could mitigate the establishment of the released Wolbachia strain in the mosquito population. Our results suggest that mitigation may be achieved through the application of a sterile insect technique. Our simulations indicate that these interventions do not override the intended wild type suppression of the IIT approach. These findings will inform policy makers of possible ways to mitigate the potential establishment of Wolbachia using the IIT population control strategy.
Simple, sensitive, and cost-effective detection of wAlbB Wolbachia in Aedes mosquitoes, using loop mediated isothermal amplification combined with the electrochemical biosensing method
22480P. Thayanukul, B. Lertanantawong, W. Sirawaraporn, S. Charasmongkolcharoen, T. Chaibun, R. Jittungdee and P. Kittayapong, PLOS Neglected Tropical Diseases, 16:e0009600. 2022-05-13 07:05:35.
Author summary Mosquito-borne diseases such as dengue, chikungunya, zika, and yellow fever are transmitted to humans mainly by the bites of Aedes aegypti mosquitoes. Controlling the vectors of these diseases relies mostly on the use of insecticides. However, the efficiency has been reduced through the development of insecticide resistance in mosquitoes. Wolbachia is an endosymbiotic bacterium that is naturally found in 40% of insects, including mosquitoes. The bacterium can protect its insect hosts from viral infections and can also cause sterility in insect host populations, therefore, providing an opportunity to use it for human disease control. Application of a Wolbachia trans-infected mosquitoes needs simple, rapid and sensitive methods for detecting the bacteria in released mosquitoes. In this paper, we develop the methods of LAMP and BIOSENSORS for detecting wAlbB Wolbachia in mosquitoes. Our positive LAMP reaction can be visualized by color change from violet to blue at a sensitivity of ≥ 10 pg of genomic DNA. When used in combination with the BIOSENSOR method, the sensitivity increases a millionfold without losing specificity. Our study suggests that both developed methods, either used in combination or stand-alone, are efficient and cost-effective, hence, they could be applied for routine surveys of Wolbachia in mosquito control programs that use Wolbachia-based approaches.
Local adaptation of Aedes aegypti mosquitoes to Wolbachia-induced fitness costs
22208P. A. Ross and A. A. Hoffmann, bioRxiv, 2022.05.06.490959. 2022-05-06 15:19:41.
Aedes aegypti mosquito eggs can remain quiescent for many months before hatching, allowing populations to persist through unfavorable conditions. Aedes aegypti infected with the Wolbachia strain wMel have been released in tropical and subtropical regions for dengue control. wMel reduces the viability of quiescent eggs, but this physiological cost might be expected to evolve in natural mosquito populations that frequently experience stressful conditions. We therefore compared the costs of wMel infection for quiescent egg viability in field-derived and laboratory populations. Quiescent egg viability was highly variable in wMel-infected populations, with greater costs of wMel in field-derived populations. In contrast, there was little variation between matched field-derived and long-term laboratory populations lacking wMel, suggesting that laboratory adaptation does not influence this trait and that differences are due to wMel infection. Comparisons of populations collected a year apart show a decline in costs under laboratory rearing conditions involving a rapid turnover of mosquito generations; this pattern was consistent across populations despite their origin, suggesting adaptation of mosquitoes to the wMel infection under laboratory conditions. Reciprocal crossing experiments confirm that differences in quiescent egg viability were mainly due to the genetic background and not Wolbachia alone. wMel-infected mosquitoes hatching from long-term quiescent eggs showed partial loss of cytoplasmic incompatibility and female infertility, highlighting additional costs of long-term quiescence. Our study provides the first evidence for a shift in Wolbachia phenotypic effects following deliberate field release and establishment and it highlights interactions between Wolbachia infections and local adaptation. The unexpected changes in fitness costs observed here suggest potential tradeoffs with undescribed fitness benefits of the wMel infection.Competing Interest StatementThe authors have declared no competing interest.
Transient Introgression of Wolbachia into Aedes aegypti Populations Does Not Elicit an Antibody Response to Wolbachia Surface Protein in Community Members
22655E. Lee, T. Hien Nguyen, T. Yen Nguyen, S. Nam Vu, N. Duong Tran, L. Trung Nghia, Q. Mai Vien, T. Dong Nguyen, R. Kriiger Loterio, I. Iturbe-Ormaetxe, H. A. Flores, S. L. O'Neill, D. Anh Dang, C. P. Simmons and J. E. Fraser, Pathogens, 11. 2022-05-03 06:41:58.
Wolbachia is an endosymbiotic bacterium that can restrict the transmission of human pathogenic viruses by Aedes aegypti mosquitoes. Recent field trials have shown that dengue incidence is significantly reduced when Wolbachia is introgressed into the local Ae. aegypti population. Female Ae. aegypti are anautogenous and feed on human blood to produce viable eggs. Herein, we tested whether people who reside on Tri Nguyen Island (TNI), Vietnam developed antibodies to Wolbachia Surface Protein (WSP) following release of Wolbachia-infected Ae. aegypti, as a measure of exposure to Wolbachia. Paired blood samples were collected from 105 participants before and after mosquito releases and anti-WSP titres were measured by ELISA. We determined no change in anti-WSP titres after ~30 weeks of high levels of Wolbachia-Ae. aegypti on TNI. These data suggest that humans are not exposed to the major Wolbachia surface antigen, WSP, following introgression of Wolbachia-infected Ae. aegypti mosquitoes.
International shipments of Wolbachia-infected mosquito eggs: towards the scaling-up of World Mosquito Program operations
23390J. A. Denton, D. A. Joubert, A. A. Goundar and J. R. L. Gilles, Scientific and Technical Review, 41:91-99. 2022-05-01 08:01:14.
The Wolbachia insect control method, employed by the World Mosquito Program (WMP), relies on introgressing Wolbachia through target Aedes aegypti populations to reduce the incidence of dengue. Since 2010, the WMP has been producing Wolbachia-infected mosquitoes at numerous sites across the globe for release in 11 countries. As the technology has matured, greater focus has been placed on mosquito production at larger central facilities for transport to remote release sites, both domestically and internationally. Of particular note is the production of Wolbachia-infected mosquitoes at the WMP's Australian production facility for successful international deployments in Fiji, Vanuatu, Kiribati and Sri Lanka. This requires careful management of both production and supply-chain processes to ensure that the quality of the mosquito eggs, specifically the hatch rate and Wolbachia infection rate, is maintained. To ensure the cost-effectiveness and scalability of the Wolbachia method, these processes will be further refined to facilitate deployment from large centralised production facilities.
Pilot trial using mass field-releases of sterile males produced with the incompatible and sterile insect techniques as part of integrated Aedes aegypti control in Mexico
22224A. Martín-Park, A. Che-Mendoza, Y. Contreras-Perera, S. Pérez-Carrillo, H. Puerta-Guardo, J. Villegas-Chim, G. Guillermo-May, A. Medina-Barreiro, H. Delfín-González, R. Méndez-Vales, S. Vázquez-Narvaez, J. Palacio-Vargas, F. Correa-Morales, G. Ayora-Tal, PLoS Negl Trop Dis, 16:e0010324. 2022-04-26 15:46:43.
We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0-75.2% suppression). CONCLUSIONS/SIGNIFICANCE: Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.
Wolbachia endosymbionts in two Anopheles species indicates independent acquisitions and lack of prophage elements
21788S. Quek, L. Cerdeira, C. L. Jeffries, S. Tomlinson, T. Walker, G. L. Hughes and E. Heinz, Microbial Genomics, 8. 2022-04-21 06:52:58.
Wolbachia is a genus of obligate bacterial endosymbionts that infect a diverse range of arthropod species as well as filarial nematodes, with its single described species, Wolbachia pipientis, divided into several ‘supergroups’ based on multilocus sequence typing. Wolbachia strains in mosquitoes have been shown to inhibit the transmission of human pathogens, including Plasmodium malaria parasites and arboviruses. Despite their large host range, Wolbachia strains within the major malaria vectors of the Anopheles gambiae and Anopheles funestus complexes appear at low density, established solely on PCR-based methods. Questions have been raised as to whether this represents a true endosymbiotic relationship. However, recent definitive evidence for two distinct, high-density strains of supergroup B Wolbachia within Anopheles demeilloni and Anopheles moucheti has opened exciting possibilities to explore naturally occurring Wolbachia endosymbionts in Anopheles for biocontrol strategies to block Plasmodium transmission. Here, we utilize genomic analyses to demonstrate that both Wolbachia strains have retained all key metabolic and transport pathways despite their smaller genome size, with this reduction potentially attributable to degenerated prophage regions. Even with this reduction, we confirmed the presence of cytoplasmic incompatibility (CI) factor genes within both strains, with wAnD maintaining intact copies of these genes while the cifB gene was interrupted in wAnM, so functional analysis is required to determine whether wAnM can induce CI. Additionally, phy logenetic analysis indicates that these Wolbachia strains may have been introduced into these two Anopheles species via horizontal transmission events, rather than by ancestral acquisition and subsequent loss events in the Anopheles gambiae species complex. These are the first Wolbachia genomes, to our knowledge, that enable us to study the relationship between natural strain Plasmodium malaria parasites and their anopheline hosts.
Aedes aegypti abundance and insecticide resistance profiles in the applying Wolbachia to eliminate dengue trial
21790W. Tantowijoyo, S. K. Tanamas, I. Nurhayati, S. Setyawan, N. Budiwati, I. Fitriana, I. Ernesia, D. S. Wardana, E. Supriyati, E. Arguni, Y. Meitika, E. Prabowo, B. Andari, B. R. Green, L. Hodgson, E. Rancès, P. A. Ryan, S. L. O'Neill, K. L. Anders, M. R. A, PLOS Neglected Tropical Diseases, 16:e0010284. 2022-04-20 07:01:27.
The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.
A metapopulation approach to identify targets for Wolbachia-based dengue control
22221A. Reyna-Lara, D. Soriano-Paños, J. H. Arias-Castro, H. J. Martínez and J. Gómez-Gardeñes, Chaos, 32:041105. 2022-04-18 15:42:29.
Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.
Environmental factors influence the local establishment of Wolbachia in Aedes aegypti mosquitoes in two small communities in central Vietnam [version 2]
21728N. T. Hien, D. D. Anh, N. H. Le, N. T. Yen, T. V. Phong, V. S. Nam, T. N. Duong, N. B. Nguyen, D. T. T. Huong, L. Q. Hung, C. N. T. Trinh, N. V. Hoang, V. Q. Mai, L. T. Nghia, N. T. Dong, L. H. Tho, S. Kutcher, T. P. Hurst, J. L. Montgomery, M. Woolfit, E, Gates Open Research, 5:147. 2022-04-18 09:54:42.
Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown to reduce transmission of dengue and other pathogens, under both laboratory and field conditions. Here we describe the entomological outcomes of wMel Wolbachia mosquito releases in two small communities in Nha Trang City in central Vietnam. Methods: The wMel strain of Wolbachia was backcrossed into local Aedes aegypti genotype and mosquito releases were undertaken by community members or by staff. Field monitoring was undertaken to track Wolbachia establishment in local Ae. aegypti mosquito populations. Ecological studies were undertaken to assess relationships between environmental factors and the spatial and temporal variability in Wolbachia infection prevalence in mosquitoes. Results: Releases of wMel Wolbachia Ae. aegypti mosquitoes in two small communities in Nha Trang City resulted in the initial establishment of Wolbachia in the local Ae. aegypti mosquitopopulations, followed by seasonal fluctuations in Wolbachia prevalence. There was significant small-scale spatial heterogeneity in Wolbachia infection prevalence in the Tri Nguyen Village site, resulting in the loss of wMel Wolbachia infection in mosquitoes in north and center areas, despite Wolbachia prevalence remaining high in mosquitoes in the south area. In the second site, Vinh Luong Ward, Wolbachia has persisted at a high level in mosquitoes throughout this site despite similar seasonal fluctuations in wMel Wolbachia prevalence. Conclusion: Seasonal variation in Wolbachia infection prevalence in mosquitoes was associated with elevated temperature conditions, and was possibly due to imperfect maternal transmission of Wolbachia. Heterogeneity in Wolbachia infection prevalence was found throughout one site, and indicates additional factors may influence Wolbachia establishment.
Mathematical modelling to assess the feasibility of Wolbachia in malaria vector biocontrol
22650S. Andreychuk and L. Yakob, Journal of Theoretical Biology, 542. 2022-03-29 06:30:06.
Releasing mosquitoes transinfected with the endosymbiotic bacterium Wolbachia is a novel strategy for interrupting vector-borne pathogen transmission. Following its success in controlling arboviruses spread by Aedes aegypti, this technology is being adapted for anopheline malaria vectors. However, antagonistic interactions between Wolbachia and naturally resident Asaia bacteria in malaria vectors have been demonstrated experimentally, potentially jeopardising Wolbachia biocontrol. We developed the first mathematical model accounting for interspecific competition between endosymbionts to assess the feasibility of this novel strategy for controlling malaria. First, Asaia prevalences among natural mosquito populations were compared with simulations parametrized with rates of Asaia transmission reported from laboratory studies. Discrepancies between projections and natural Asaia prevalences indicated potential overestimation of Asaia transmissibility in artificial laboratory settings. With parametrization that matches natural Asaia prevalence, simulations identified redundancies in Asaia's many infection routes (vertical, sexual and environmental). This resilience was only overcome when Wolbachia conferred very high resistance to environmental infection with Asaia, resulting in Wolbachia fixation and Asaia exclusion. Wolbachia's simulated spread was prevented when its maternal transmission was impeded in coinfected mosquitoes and the pre-control Asaia prevalence was beyond a threshold of 60-75%. This theoretical assessment highlights critical next steps in laboratory experiments to inform this strategy's feasibility. (c) 2022 The Author(s). Published by Elsevier Ltd.
Cytoplasmic incompatibility: A Wolbachia toxin–antidote mechanism comes into view
21546M. Hochstrasser, Current Biology, 32:R287-R289. 2022-03-28 11:56:01.
The Wolbachia cidA and cidB genes promote bacterial endosymbiont inheritance through the host female germline. CidB is now shown to load into maturing sperm nuclei. Following fertilization, it disrupts paternal chromosome condensation, triggering embryonic arrest if not countered by CidA in Wolbachia-infected eggs.
Special mosquitos to combat dengue fever in Binh Duong
21249L. Phuong, VN Express, 2022-03-25 08:39:12.
Capsules containing mosquito eggs resistant to dengue fever viruses were released in southern Binh Duong's Thu Dau Mot Town on Thursday to help control the disease. The Wolbachia Project in southern Vietnam, conducted by the World Mosquito Program and collaborators, seeks to release mosquitos infected with the Wolbachia bacteria into the environment. The bacteria, a natural pathogen to several insects, would compete with viruses like dengue, Zika, chikungunya and yellow fever found inside mosquitos, thus making it harder for viruses to replicate and for mosquitos to spread the viruses to humans.
Symbionts and gene drive: two strategies to combat vector-borne disease
21029G.-H. Wang, J. Du, C. Y. Chu, M. Madhav, G. L. Hughes and J. Champer, Trends in Genetics, 2022-03-18 07:56:11.
Mosquitoes bring global health problems by transmitting parasites and viruses such as malaria and dengue. Unfortunately, current insecticide-based control strategies are only moderately effective because of high cost and resistance. Thus, scalable, sustainable, and cost-effective strategies are needed for mosquito-borne disease control. Symbiont-based and genome engineering-based approaches provide new tools that show promise for meeting these criteria, enabling modification or suppression approaches. Symbiotic bacteria like Wolbachia are maternally inherited and manipulate mosquito host reproduction to enhance their vertical transmission. Genome engineering-based gene drive methods, in which mosquitoes are genetically altered to spread drive alleles throughout wild populations, are also proving to be a potentially powerful approach in the laboratory. Here, we review the latest developments in both symbionts and gene drive-based methods. We describe some notable similarities, as well as distinctions and obstacles, relating to these promising technologies.
Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods
20977T. Bhattacharya, L. Yan, J. M. Crawford, H. Zaher, I. L. G. Newton and R. W. Hardy, PLoS Pathogens, 18:e1010393. 2022-03-16 07:40:04.
Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia-induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia-colonized animals, coincident with reduced virus replication and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells is proviral, increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity is dependent on its methyltransferase activity. Finally, examining the effects of Wolbachia on modifications of viral RNA by LC-MS show a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is a vital mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental alphavirus replication and transmission processes.
Wolbachia wAlbB inhibits bluetongue and epizootic hemorrhagic fever viruses in Culicoides midge cells
20630M. L. Matthews, H. O. Covey, B. S. Drolet and C. L. Brelsfoard, Medical and Veterinary Entomology, 2022-03-10 07:56:14.
Abstract Culicoides midges are hematophagous insects that transmit arboviruses of veterinary importance. These viruses include bluetongue virus (BTV) and epizootic hemorrhagic fever virus (EHDV). The endosymbiont Wolbachia pipientis Hertig spreads rapidly through insect host populations and has been demonstrated to inhibit viral pathogen transmission in multiple mosquito vectors. Here, we have demonstrated a replication inhibitory effect on BTV and EHDV in a Wolbachia (wAlbB strain)-infected Culicoides sonorensis Wirth and Jones W8 cell line. Viral replication was significantly reduced by day 5 for BTV and by day 2 for EHDV as detected by real-time polymerase chain reaction (RT-qPCR) of the non-structural NS3 gene of both viruses. Evaluation of innate cellular immune responses as a cause of the inhibitory effect showed responses associated with BTV but not with EHDV infection. Wolbachia density also did not play a role in the observed pathogen inhibitory effects, and an alternative hypothesis is suggested. Applications of Wolbachia-mediated pathogen interference to impact disease transmission by Culicoides midges are discussed.
EVITA Dengue: a cluster-randomized controlled trial to EValuate the efficacy of Wolbachia-InfecTed Aedes aegypti mosquitoes in reducing the incidence of Arboviral infection in Brazil
20526M. H. Collins, G. E. Potter, M. D. T. Hitchings, E. Butler, M. Wiles, J. K. Kennedy, S. B. Pinto, A. B. M. Teixeira, A. Casanovas-Massana, N. G. Rouphael, G. A. Deye, C. P. Simmons, L. A. Moreira, M. L. Nogueira, D. A. T. Cummings, A. I. Ko, M. M. Teixeir, Trials, 23:185. 2022-03-02 08:20:38.
BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.
Increased biting rate and decreased Wolbachia density in irradiated Aedes mosquitoes
20487R. Moretti, E. Lampazzi, C. Damiani, G. Fabbri, G. Lombardi, C. Pioli, A. Desiderio, A. Serrao and M. Calvitti, Parasites and Vectors, 15:67. 2022-02-24 08:48:28.
Releasing considerable numbers of radiation-sterilized males is a promising strategy to suppress mosquito vectors. However, releases may also include small percentages of biting females, which translate to non-negligible numbers when releases are large. Currently, the effects of irradiation on host-seeking and host-biting behaviors have not been exhaustively investigated. Information is also lacking regarding the effects of sterilizing treatment on the endosymbiotic bacterium Wolbachia, which is known to affect the vector competence of infected mosquitos.
Wolbachia in Aedes koreicus: Rare Detections and Possible Implications
20475C. Damiani, A. Cappelli, F. Comandatore, F. Montarsi, A. Serrao, A. Michelutti, M. Bertola, M. V. Mancini, I. Ricci, C. Bandi and G. Favia, Insects, 13. 2022-02-21 08:21:51.
The emerging distribution of new alien mosquito species was recently described in Europe. In addition to the invasion of Aedes albopictus, several studies have focused on monitoring and controlling other invasive Aedes species, as Aedes koreicus and Aedes japonicus. Considering the increasing development of insecticide resistance in Aedes mosquitoes, new control strategies, including the use of bacterial host symbionts, are proposed. However, little is known about the bacterial communities associated with these species, thus the identification of possible candidates for Symbiotic Control is currently limited. The characterization of the natural microbiota of field-collected Ae. koreicus mosquitoes from North-East Italy through PCR screening, identified native infections of Wolbachia in this species that is also largely colonized by Asaia bacteria. Since Asaia and Wolbachia are proposed as novel tools for Symbiotic Control, our study supports their use for innovative control strategies against new invasive species. Although the presence of Asaia was previously characterized in Ae. koreicus, our study characterized this Wolbachia strain, also inferring its phylogenetic position. The co-presence of Wolbachia and Asaia may provide additional information about microbial competition in mosquito, and to select suitable phenotypes for the suppression of pathogen transmission and for the manipulation of host reproduction in Ae. koreicus.
Wolbachia Impacts Anaplasma Infection in Ixodes scapularis Tick Cells
20436K. M. Skinner, J. Underwood, A. Ghosh, A. S. Oliva Chavez and C. L. Brelsfoard, International Journal of Environmental Research and Public Health, 19. 2022-02-16 08:58:32.
The specific interactions of members of tick bacterial microbiota and their effects on pathogen transmission remains relatively unexplored. Here, we introduced a novel Wolbachia infection type into Ixodes scapularis tick cells and examined the antipathogenic effects on the intracellular pathogen Anaplasma phagocytophilum. An increase in A. phagocytophilum replication was observed in Wolbachia-infected tick cells. However, Wolbachia infection densities decreased when cells were serially passaged and ultimately the infection was lost. Host-cell immune response was also examined as an additional factor that could have affected A. phagocytophilum replication in Wolbachia-infected cells. In early passages post-Wolbachia infection, a decreased immune response was observed, but in later passages of cells with low Wolbachia densities, there was no change in the immune response. The results are discussed in relation to the importance of studying the interactions of the tick microbiota, the host cell, and the pathogen and the development of novel tick and tick-borne disease-control approaches.
Uniqueness and stability of periodic solutions for an interactive wild and Wolbachia-infected male mosquito model
20438R. Yan and Q. Sun, Journal of Biological Dynamics, 2022-02-15 09:03:48.
We investigate a mosquito population suppression model, which includes the release of Wolbachia-infected males causing incomplete cytoplasmic incompatibility (CI). The model consists of two sub-equations by considering the density-dependent birth rate of wild mosquitoes. By assuming the release waiting period T is larger than the sexual lifespan T¯ of Wolbachia-infected males, we derive four thresholds: the CI intensity threshold sh∗, the release amount thresholds g∗ and c∗, and the waiting period threshold T∗. From a biological view, we assume sh > sh∗ throughout the paper. When g∗ < c < c∗, we prove the origin E0 is locally asymptotically stable iff T < T∗, and the model admits a unique T-periodic solution iff T ≥ T∗, which is globally asymptotically stable. When c ≥ c∗, we show the origin E0 is globally asymptotically stable iff T ≤ T∗, and the model has a unique T-periodic solution iff T > T∗, which is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations.
Quality over quantity: unraveling the contributions to cytoplasmic incompatibility caused by two coinfecting Cardinium symbionts
20317M. R. Doremus, C. M. Stouthamer, S. E. Kelly, S. Schmitz-Esser and M. S. Hunter, Heredity, 2022-02-05 09:08:33.
Cytoplasmic incompatibility (CI) is a common form of reproductive sabotage caused by maternally inherited bacterial symbionts of arthropods. CI is a two-step manipulation: first, the symbiont modifies sperm in male hosts which results in the death of fertilized, uninfected embryos. Second, when females are infected with a compatible strain, the symbiont reverses sperm modification in the fertilized egg, allowing offspring of infected females to survive and spread the symbiont to high frequencies in a population. Although CI plays a role in arthropod evolution, the mechanism of CI is unknown for many symbionts. Cardinium hertigii is a common CI-inducing symbiont of arthropods, including parasitoid wasps like Encarsia partenopea. This wasp harbors two Cardinium strains, cEina2 and cEina3, and exhibits strong CI. The strains infect wasps at different densities, with the cEina3 present at a lower density than cEina2, and it was previously not known which strain caused CI. By differentially curing wasps of cEina3, we found that this low-density symbiont is responsible for CI and modifies males during their pupal stage. cEina2 does not modify host reproduction and may spread by ‘hitchhiking’ with cEina3 CI or by conferring an unknown benefit. The cEina3 strain also shows a unique localization pattern in male reproductive tissues. Instead of infecting sperm like other CI-inducing symbionts, cEina3 cells are found in somatic cells at the testis base and around the seminal vesicle. This may allow the low-density cEina3 to efficiently modify host males and suggests that cEina3 uses a different modification strategy than sperm-infecting CI symbionts.
Endosymbionts moderate constrained sex allocation in a haplodiploid thrips species in a temperature-sensitive way
20394A. Katlav, D. T. Nguyen, J. L. Morrow, R. N. Spooner-Hart and M. Riegler, Heredity, 9. 2022-02-03 09:32:33.
Maternally inherited bacterial endosymbionts that affect host fitness are common in nature. Some endosymbionts colonise host populations by reproductive manipulations (such as cytoplasmic incompatibility; CI) that increase the reproductive fitness of infected over uninfected females. Theory predicts that CI-inducing endosymbionts in haplodiploid hosts may also influence sex allocation, including in compatible crosses, however, empirical evidence for this is scarce. We examined the role of two common CI-inducing endosymbionts, Cardinium and Wolbachia, in the sex allocation of Pezothrips kellyanus, a haplodiploid thrips species with a split sex ratio. In this species, irrespective of infection status, some mated females are constrained to produce extremely male-biased broods, whereas other females produce extremely female-biased broods. We analysed brood sex ratio of females mated with males of the same infection status at two temperatures. We found that at 20 degrees C the frequency of constrained sex allocation in coinfected pairs was reduced by 27% when compared to uninfected pairs. However, at 25 degrees C the constrained sex allocation frequency increased and became similar between coinfected and uninfected pairs, resulting in more male-biased population sex ratios at the higher temperature. This temperature-dependent pattern occurred without changes in endosymbiont densities and compatibility. Our findings indicate that endosymbionts affect sex ratios of haplodiploid hosts beyond the commonly recognised reproductive manipulations by causing female-biased sex allocation in a temperature-dependent fashion. This may contribute to a higher transmission efficiency of CI-inducing endosymbionts and is consistent with previous models that predict that CI by itself is less efficient in driving endosymbiont invasions in haplodiploid hosts.
Assessing Aedes aegypti candidate genes during viral infection and Wolbachia-mediated pathogen blocking
20315L. T. Sigle, M. Jones, M. Novelo, S. A. Ford, N. Urakova, K. Lymperopoulos, R. T. Sayre, Z. Xi, J. L. Rasgon and E. A. McGraw, Insect Molecular Biology, 2022-02-03 09:03:09.
Abstract One approach to control dengue virus transmission is the symbiont Wolbachia, that limits viral infection in mosquitoes. Despite plans for its widespread use in Aedes aegypti, Wolbachia's mode of action remains poorly understood. Many studies suggest that the mechanism is likely multifaceted, involving aspects of immunity, cellular stress, and nutritional competition. A previous study from our group used artificial selection to identify a new mosquito candidate gene related to viral blocking; alpha-mannosidase-2a (alpha-Mann-2a) with a predicted role in protein glycosylation. Protein glycosylation pathways tend to be involved in complex host-viral interactions; however, the function of alpha-mannosidases has not been described in mosquito-virus interactions. We examined alpha-Mann-2a expression in response to virus and Wolbachia infections and whether reduced gene expression, caused by RNA interference (RNAi), affected viral loads. We show that dengue virus (DENV) infection affects the expression of alpha-Mann-2a in a tissue- and time-dependent manner, whereas Wolbachia infection had no effect. In the midgut, DENV prevalence increased following knockdown of alpha-Mann-2a expression in Wolbachia-free mosquitoes, suggesting that alpha-Mann-2a interferes with infection. Expression knockdown had the same effect on the togavirus chikungunya virus (CHIKV), indicating that alpha-Mann-2a may have broad antivirus effects in the midgut. Interestingly, we were unable to knockdown the expression in Wolbachia-infected mosquitoes. We also provide evidence that alpha-Mann-2a may affect the transcriptional level of another gene predicted to be involved in viral blocking and cell adhesion; cadherin87a. These data support the hypothesis that glycosylation and adhesion pathways may broadly be involved in viral infection in Ae. aegypti. This article is protected by copyright. All rights reserved.
Paternal transmission of the Wolbachia CidB toxin underlies cytoplasmic incompatibility
20434B. Horard, K. Terretaz, A. S. Gosselin-Grenet, H. Sobry, M. Sicard, F. Landmann and B. Loppin, Current Biology, 2022-02-01 08:53:36.
Wolbachia are widespread endosymbiotic bacteria that manipulate the reproduction of arthropods through a diversity of cellular mechanisms. In cytoplasmic incompatibility (CI), a sterility syndrome originally discovered in the mosquito Culex pipiens, uninfected eggs fertilized by sperm from infected males are selectively killed during embryo development following the abortive segregation of paternal chromosomes in the zygote. Despite the recent discovery of Wolbachia CI factor (cif) genes, the mechanism by which they control the fate of paternal chromosomes at fertilization remains unknown. Here, we have analyzed the cytological distribution and cellular impact of CidA and CidB, a pair of Cif proteins from the Culex-infecting Wolbachia strain wPip. We show that expression of CidB in Drosophila S2R+ cells induces apoptosis unless CidA is co-expressed and associated with its partner. In transgenic Drosophila testes, both effectors colocalize in germ cells until the histone-to-protamine transition in which only CidB is retained in maturing spermatid nuclei. We further show that CidB is similarly targeted to maturing sperm of naturally infected Culex mosquitoes. At fertilization, CidB associates with paternal DNA regions exhibiting DNA replication stress, as a likely cause of incomplete replication of paternal chromosomes at the onset of the first mitosis. Importantly, we demonstrate that inactivation of the deubiquitylase activity of CidB does not abolish its cell toxicity or its ability to induce CI in Drosophila. Our study thus demonstrates that CI functions as a transgenerational toxin-antidote system and suggests that CidB acts by poisoning paternal DNA replication in incompatible crosses.
Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species
20177G. Rašić, N. F. Lobo, E. H. Jeffrey Gutiérrez, C. H. Sánchez and J. M. Marshall, Frontiers in Genetics, 12:780327. 2022-01-25 09:18:49.
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resistance mechanisms and non-functional effector genes that spread within trial and intervention sites. This is of particular importance for non-localized gene drive projects, as the potential scale of intervention means that monitoring is expected to be more costly than research, development and deployment. Regarding monitoring needs for population replacement systems, lessons may be learned from experiences with Wolbachia-infected mosquitoes, and for population suppression systems, from experiences with releases of genetically sterile male mosquitoes. For population suppression systems, assessing monitoring requirements for tracking population size and detecting rare resistant alleles are priorities, while for population replacement systems, allele frequencies must be tracked, and pressing concerns include detection of gene drive alleles with non-functional effector genes, and resistance of pathogens to functional effector genes. For spread to unintended areas, open questions relate to the optimal density and placement of traps and frequency of sampling in order to detect gene drive alleles, drive-resistant alleles or non-functional effector genes while they can still be effectively managed. Invasive species management programs face similar questions, and lessons may be learned from these experiences. We explore these monitoring needs for gene drive mosquito projects progressing through the phases of pre-release, release and post-release.
Recently introduced Wolbachia reduces bacterial species richness and reshapes bacterial community structure in Nilaparvata lugens
20141T.-P. Li, C.-Y. Zhou, J.-T. Gong, Z. Xi and X.-Y. Hong, Pest Management Science, 2022-01-21 13:28:22.
BACKGROUND Wolbachia has been developed as an effective tool to suppress insect pests and arbovirus transmission. Recently, the brown planthopper Nilaparvata lugens, a serious agricultural pest, has been successfully transinfected with Wolbachia strain wStri from Laodelphax striatellus. However, before conducting the field experiments, the impacts of wStri on the bacterial microbiota in N. lugens and how it differs from native Wolbachia wLug strain have not been clarified. RESULTS Here, we found that wStri reduced bacterial diversity and shaped bacterial community structure more than wLug in both developmental stage and different adult tissues. Overall, the relative abundance of Wolbachia was negatively correlated with bacterial diversity, but the bacterial diversity gradually decreased only when the relative abundance of Wolbachia was higher than 60%. Further analysis found that wStri reduced species richness of other bacteria but not their evenness. wStri infection also affected many bacterial functions (e.g., amino acid metabolism & signaling and cellular processes) in the developmental stages, with a stronger effect than wLug in nymphs. Moreover, although Wolbachia occupied a high relative abundance in infected individuals, Acinetobacter was consistently a core part of microbiome. CONCLUSION These results showed the significant impacts of recently introduced wStri on bacterial microbiota in N. lugens, with the effects differing from native wLug. This study will aid in understanding the relationship between Wolbachia, its host and the host's microbiota, and provide a reference for future field experiments. This article is protected by copyright. All rights reserved.
Characterization of the first Wolbachia from the genus Scaptodrosophila, a male-killer from the rainforest species S. claytoni
20034K. M. Richardson, M. Schiffer, P. A. Ross, J. A. Thia and A. A. Hoffmann, Insect Science, 2022-01-12 09:30:05.
Abstract The Scaptodrosophila genus represents a large group of drosophilids with a worldwide distribution and a predominance of species in Australia, but there is little information on the presence and impacts of Wolbachia endosymbionts in this group. Here we describe the first Wolbachia infection from this group, wClay isolated from Scaptodrosophila claytoni (van Klinken), a species from the east coast of Australia. The infection is polymorphic in natural populations, occurring at a frequency of around 6%?10%. wClay causes male killing, producing female-biased lines; most lines showed 100% male killing, though in one line it was < 80%. The lines need to be maintained through the introduction of males unless the infection is removed by tetracycline treatment. wClay is transmitted at a high fidelity (98.6%) through the maternal lineage and has been stable in two laboratory lines across 24 generations, suggesting it is likely to persist in populations. The infection has not been previously described but is closely related to the male-killing Wolbachia recently described from Drosophila pandora based on MLST typing and the wsp gene. Male-killing Wolbachia are likely to be common in drosophilids but remain difficult to detect because the infections can often be at a low frequency. This article is protected by copyright. All rights reserved
Lab-scale characterization and semi-field trials of Wolbachia Strain wAlbB in a Taiwan Wolbachia introgressed Ae. aegypti strain
20383W. L. Liu, H. Y. Yu, Y. X. Chen, B. Y. Chen, S. N. Leaw, C. H. Lin, M. P. Su, L. S. Tsai, Y. Chen, S. H. Shiao, Z. Y. Xi, A. C. C. Jang and C. H. Chen, PLOS Neglected Tropical Diseases, 16:24. 2022-01-11 08:53:33.
Author summaryPrior to open field release, new genetic approaches that interfere with mosquito abilities and reduce mosquito population density require progressive evaluation both in the laboratory and contained field trials. Trials in contained outdoor systems are thus an important step and allow for evaluation of the effectiveness and reliability of Wolbachia-infected Aedes aegypti (wAlbB-Tw) in settings that incorporate natural environmental variations. We describe a semi-field system designed to study the ability of wAlbB-Tw mosquitoes to suppress local mosquito populations. We provide a protocol for establishing, maintaining, and monitoring Ae. aegypti population densities inside field cages. These results pave the way for the open release of wAlbB-Tw-infected Ae. aegypti mosquitoes in the field. Dengue fever is one of the most severe viral diseases transmitted by Aedes mosquitoes, with traditional approaches of disease control proving insufficient to prevent significant disease burden. Release of Wolbachia-transinfected mosquitoes offers a promising alternative control methodologies; Wolbachia-transinfected female Aedes aegypti demonstrate reduced dengue virus transmission, whilst Wolbachia-transinfected males cause zygotic lethality when crossed with uninfected females, providing a method for suppressing mosquito populations. Although highly promising, the delicate nature of population control strategies and differences between local species populations means that controlled releases of Wolbachia-transinfected mosquitoes cannot be performed without extensive testing on specific local Ae. aegypti populations. In order to investigate the potential for using Wolbachia to suppress local Ae. aegypti populations in Taiwan, we performed lab-based and semi-field fitness trials. We first transinfected the Wolbachia strain wAlbB into a local Ae. aegypti population (wAlbB-Tw) and found no significant changes in lifespan, fecundity and fertility when compared to controls. In the laboratory, we found that as the proportion of released male mosquitoes carrying Wolbachia was increased, population suppression could reach up to 100%. Equivalent experiments in semi-field experiments found suppression rates of up to 70%. The release of different ratios of wAlbB-Tw males in the semi-field system provided an estimate of the optimal size of male releases. Our results indicate that wAlbB-Tw has significant potential for use in vector control strategies aimed at Ae. aegypti population suppression in Taiwan. Open field release trials are now necessary to confirm that wAlbB-Tw mediated suppression is feasible in natural environments.
Cytoplasmic incompatibility in hybrid zones: infection dynamics and resistance evolution
19742E. S. Røed and J. Engelstädter, Journal of Evolutionary Biology, 2021-12-25 13:16:15.
Cytoplasmic incompatibility is an endosymbiont-induced mating incompatibility common in arthropods. Unidirectional cytoplasmic incompatibility impairs crosses between infected males and uninfected females, whereas bidirectional cytoplasmic incompatibility occurs when two host lineages are infected with reciprocally in compatible endosymbionts. Bidirectional cytoplasmic incompatibility is unstable in unstructured populations, but may be stable in hybrid zones. Stable coexistence of incompatible host lineages should generate frequent incompatible crosses. Therefore, hosts are expected to be under selection to resist their endosymbionts. Here, we for mulate a mathematical model of hybrid zones where two bidirectionally incompatible host lineages meet. We expand this model to consider the invasion of a hypothetical resistance allele. To corroborate our mathematical predictions, we test each prediction with stochastic, individual-based simulations. Our models suggest that hybrid zones may sustain stable coinfections of bidirectionally incompatible endosymbiont strains. Over a range of conditions, host are under selection for resistance against cytoplasmic incompatibility. Under asymetric migration, a resistance allele can facilitate infection turnover and subsequently either persist or become lost. The predictions we present may inform our understanding of the cophylogenetic relationship between the endosym biont Wolbachia and its hosts.
Determinants of stakeholders’ attitudes and intentions toward supporting the use of Wolbachia-infected Aedes mosquitoes for dengue control
19744A. F. Arham, L. Amin, M. A. C. Mustapa, Z. Mahadi, M. Yaacob and M. Ibrahim, BMC Public Health, 21:2314. 2021-12-23 13:22:08.
BACKGROUND: A recent approach in controlling dengue is by using the Wolbachia-infected Aedes mosquito (WiAM). The approach has been reported to be more effective than traditional methods, such as fogging. Therefore, it is imperative to assess the factors predicting its acceptance among stakeholders before implementing this technology more widely in Malaysia. METHODS: The survey data were collected from two primary stakeholder groups using a stratified random sampling technique. The two primary stakeholder groups were scientists (n = 202) and the public (n = 197) in the Klang Valley region of Malaysia, a hot spot area known for the high rate of dengue cases. The respondents answered questions on a seven-point Likert scale survey regarding trust in key players, attitudes toward nature versus materialism, religiosity, perceived benefits, perceived risks, attitudes, and intentions. The data were analyzed using Smart Partial Least Square (SmartPLS) software (version 3.2.6) to determine the predictors influencing attitudes and intentions to support the use of WiAM technology. RESULTS: The results indicated a strong positive relationship between attitudes and intentions to support the use of WiAM (β = 0.676, p < 0.001). The most important significant predictor for attitudes was perceived benefits (β = 0.493, p < 0.001), followed by perceived risks (β = - 0.080, p = 0.048). Trust in key players, attitudes toward nature versus material, and religiosity had indirect relationships with attitudes through the perceived benefits and risks. CONCLUSIONS: The identified predictors can serve as indicators for the decision-making process regarding WiAM implementation in Malaysia and other developing countries with similar demographics and cultures.
From Wolbachia genomics to phenotype: molecular models of cytoplasmic incompatibility must account for the multiplicity of compatibility types
19733A. Namias, M. Sicard, M. Weill and S. Charlat, Current Opinion in Insect Science, 2021-12-23 13:03:28.
Wolbachia endosymbionts commonly induce cytoplasmic incompatibility, making infected males’ sperm lethal to the embryos unless these are rescued by the same bacterium, inherited from their mother. Causal genes were recently identified but two families of mechanistic models are still opposed. In the toxin–antidote model, interaction between the toxin and the antidote is required for rescuing the embryos. In host modification models, a host factor is misregulated in sperm and rescue occurs through compensation or withdrawal of this modification. While these models have been thoroughly discussed, the multiplicity of compatibility types, that is, the existence of many mutually incompatible strains, as seen in Culex mosquitoes, has not received sufficient attention. To explain such a fact, host modification models must posit that the same embryonic defects can be induced and rescued through a large variety of host targets. Conversely, the toxin–antidote model simply accommodates this pattern in a lock–key fashion, through variations in the toxin–antidote interaction sites.
Wolbachia: Biological Control Strategy Against Arboviral Diseases
19967I. Mohanty, A. Rath and R. K. Hazra, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:27:44.
Arboviral diseases like dengue, chikungunya, and Zika are among the major causes of mortality and morbidity in human population. The limited control methods together with lack of antiviral therapies and effective vaccines have paved way for new approaches. One such approach to reduce the ever alarming conflagration of vector-borne diseases is based on biological strategy that reduces or blocks pathogen transmission in the vector. In this context, Wolbachia, an endosymbiont in mosquitoes, is explored as a novel and ecofriendly control strategy. Wolbachia seems to confer resistance to diverse RNA viruses protecting lives from virus-induced mortality. This review envisages the deployment of Wolbachia technology in controlling several arboviral diseases.
Wolbachia Endosymbiont and Mosquito Vectors, with Emphasis on Lymphatic Filariasis Elimination
19965I. P. Sunish, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:24:11.
Wolbachia are maternally inherited intracellular bacteria, known to alter early development and mitotic processes in their hosts. They are frequently observed as a reproductive parasite, capable of inducing feminization, parthenogenesis, male killing, or cytoplasmic incompatibility. A total of 18 clades of Wolbachia have been reported, almost exclusively in arthropods. Wolbachia-based strategies have been proposed for the control of disease vectors. Wolbachia-based population suppression and transmission blocking can work in species not commonly infected with Wolbachia in the wild. However, efficient maintenance and spread of Wolbachia infection into field populations is crucial to the success of this strategy. Property of cytoplasmic incompatibility (CI) can be used to reduce the density of mosquito field populations through inundative releases of incompatible males in order to sterilize females. In semi-field condition at La Reunion, the LR[wPip(Is)] males of Culex quinquefasciatus successfully competed with field males in mating with field females. Depletion of Wolbachia endobacteria by antibiotic therapy prevents larval moulting and kills adult filarial worms. This strategy could act as an adjunct to vector control and is being exploited for the elimination of lymphatic filariasis.
Field Trials of Gene Drive Mosquitoes: Lessons from Releases of Genetically Sterile Males and Wolbachia-infected Mosquitoes
19925J. M. Marshall and V. N. Vásquez, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:27:08.
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiting gene drive systems to be engineered with much greater ease, including (1) threshold-dependent systems, which tend to spread only when introduced above a certain threshold population frequency, and (2) temporally self-limiting systems, which display transient drive activity before being eliminated by virtue of a fitness cost. As these CRISPR-based gene drive systems are yet to be field-tested, plenty of open questions remain to be addressed, and insights can be gained from precedents set by field trials of other novel genetics-based and biological control systems, such as trials of Wolbachia-transfected mosquitoes, intended for either population replacement or suppression, and trials of genetically sterile male mosquitoes, either using the RIDL system (release of insects carrying a dominant lethal gene) or irradiation. We discuss lessons learned from these field trials and implications for a phased exploration of gene drive technology, including homing-based gene drive, chromosomal translocations, and split gene drive as a system potentially suitable for an intermediate release.
Arthropods of Medical Importance: Need for Genetic and Other Innovative Vector Control Technologies, with Emphasis on Eco-biosocial and Environmental Considerations.
19923B. K. Tyagi, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:22:08.
Among the world’s known vector groups, viz. arthropods, snails and rodents, the most important vectors originate from arthropods, the jointed legs. Arthropods are doubtlessly regarded as the most dominant creatures on the Earth due largely to their remarkable structural and behavioural diversity, besides humongous species preponderance. Of course, some of these arthropods are serious pests and/or vectors of human and animal diseases—deadly, debilitating and economy destructing. According to an estimate, arthropod species make approximately 80% of the global biological diversity. Born some 350–400 million years ago, they have of course achieved, to the utter envy of all other animal forms, a formidable genetic diversity and robustness so much so that they have virtually captivated pivotal human attention for centuries. They serve as a spectacular model of bioprospecting or laboratory experiments mostly because they are found in abundance, breed prodigiously and are exceptionally easier to culture or cultivate. For the aforesaid reasons, arthropods are also the easy target for genetic manipulations such as the transgenesis (using the release of insect carrying dominant lethal (RIDL) gene system or gene drive-based genome editing, e.g. CRISPR/Cas9, to suppress or replace the vector population) or paratransgenesis (e.g. deploying endosymbiont Wolbachia-induced cytoplasmic incompatibility for replacing natural vector population). In particular, the advent of CRISPR technology has excited the potential to engineer new game-changing technologies and innovative systems that can be used to control wild populations of mosquitoes. Two developments of particular interest are a self-limiting system termed precision-guided sterile insect technique (pgSIT) and a homing-based gene drive (HGD). The unique features of these systems can make them valuable tools to control vector mosquitoes in the future. All these biotechnological advancements in vector control are designed to fit well in the multi-methodical integrated vector management (IVM) strategy.
The Effects of Boric Acid Sugar Bait on Wolbachia Trans-Infected Male Aedes albopictus (ZAP Males®) in Laboratory Conditions
19917V. S. Aryaprema, W. A. Qualls, K. L. Dobson, S. L. Dobson and R.-D. Xue, Insects, 13. 2021-12-21 09:06:57.
The field release of Wolbachia trans-infected male mosquitoes, as well as the use of toxic sugar baits, is a novel and promising candidate technique for integrated mosquito management programs. However, the methods of action of the two techniques may not be complementary, because the Wolbachia method releases mosquitoes into the environment expecting a wild population reduction in subsequent generations while the toxic baits are intended to reduce the wild population by killing mosquitoes. This laboratory study was conducted to evaluate the effectiveness of boric acid toxic sugar baits on Wolbachia trans-infected male Aedes albopictus, relative to wild-type Ae. albopictus males. Wolbachia trans-infected (ZAP male®) and the wild-type Ae. albopictus males were exposed separately to 1% boric acid in a 10% sucrose solution in BugDorms. In the control test, the two groups were exposed to 10% sucrose solution without boric acid. Percent mortalities were counted for 24 h, 48 h and 72 h post exposure periods. The results show that 1% boric acid toxic sugar bait can effectively kill ZAP males under laboratory conditions, and the effectiveness was significantly higher after 24 h and 48 h, compared to wild-type male Ae. albopictus. This finding will help in planning and coordinating integrated mosquito management programs, including both Wolbachia trans-infected mosquito releases and the use of toxic sugar baits against Ae. albopictus.
Genetically Modified and other Innovative Vector Control Technologies
19912B. K. Tyagi, SpringerLink, 2021-12-21 08:48:19.
This book comprehensively covers the latest development in developing and deploying the genetically modified vectors, particularly Anopheles and Aedes mosquitoes responsible for transmitting malaria parasites and dengue viruses, the most deadly and/or debilitating among all the vector-borne diseases. It is considered timely and commensurate to bring about a book dealing with the various ecological, biological and social as well as regulatory aspects for the deployment of genetically modified vectors in special context with the biosafety of humans, his associates, and the environment. Written by an array of specialists and experts in various subjects of genetically modified organisms, this book centrally addresses the (i) basic principles of the genetic manipulation of vectors and they are potential impact on human and the environment, (ii) ecological, biological, ethical, legal and social implications of the use of genetically modified vectors, (iii) identification of potential hazards; assessment and management of risks for human and environment; risk/benefit analysis, (iv) principles and practices for the assessment and management of biosecurity and biosafety in laboratories (and in the field), (v) guiding principles for creation and management of institutional or national biosafety review boards and ethics review committees, and (vi) development and application of a biosafety regulatory framework and its related legal principles at national levels for securing the development and use of vector control methods based on genetic modification strategies.
Towards Integrated Management of Dengue in Mumbai
19735P. N. Paradkar, P. R. Sahasrabudhe, M. Ghag Sawant, S. Mukherjee and K. R. Blasdell, Viruses, 13. 2021-12-04 13:10:23.
With increasing urbanisation, the dengue disease burden is on the rise in India, especially in large cities such as Mumbai. Current dengue surveillance in Mumbai includes municipal corporation carrying out specific activities to reduce mosquito breeding sites and the use of insecticides to suppress the adult mosquito populations. Clinical cases remain either underreported or misreported due to the restriction to government clinics, missing the large private health care sector. There is a need for an integrated approach to manage dengue outbreaks in Mumbai. There are various novel strategies available for use that can be utilised to improve disease detection, mosquito surveillance, and control of mosquito-borne diseases. These novel technologies are discussed in this manuscript. Given the complex ecosystem of mosquito-borne diseases in Mumbai, integrating data obtained from these technologies would support the ongoing mosquito control measures in Mumbai.
Combined sterile insect technique and incompatible insect technique: concept, study design, experience and lessons learned from a pilot suppression trial in Thailand
19367Kittayapong, P., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 16:50:12.
Climate change, rapid global transport and land use change leading to urbanization and agricultural intensification have facilitated disease emergence in vulnerable regions like Southeast Asia, and also the global expansion of vectors and vector-borne diseases into other regions like the Americas and Europe. Important vector-borne diseases, i.e. dengue, chikungunya, yellow fever, and Zika are transmitted by the major mosquito vector species, Aedes aegypti (L.) and Aedes albopictus (Skuse). Management of Ae. aegypti populations in countries endemic to these diseases, especially in Southeast Asia, is not sufficiently effective, resulting in high morbidity and mortality in the region. Insecticide resistance has become an important issue, causing failure in insecticide-based vector control. Innovative or alternative tools/approaches are needed to effectively reduce mosquito vector populations and consequently reduce the diseases they transmit. A trial integrating the environment-friendly Sterile Insect Technique (SIT) and the insect incompatible technique (IIT) was successfully carried out on a small-scale in a semi-rural setting in Thailand. In this chapter, we report on the design and methodology, as well as the experience and lessons learned from the baseline preparation and implementation of the pilot trial.
Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector
19439K. L. Adams, D. G. Abernathy, B. C. Willett, E. K. Selland, M. A. Itoe and F. Catteruccia, Nature Microbiology, 6:1575-1582. 2021-11-26 20:50:59.
Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors.
Wolbachia reduces virus infection in a natural population of Drosophila
19437R. Cogni, S. D. Ding, A. C. Pimentel, J. P. Day and F. M. Jiggins, Communications Biology, 4:1327. 2021-11-25 20:42:30.
Wolbachia is a maternally transmitted bacterial symbiont that is estimated to infect approximately half of arthropod species. In the laboratory it can increase the resistance of insects to viral infection, but its effect on viruses in nature is unknown. Here we report that in a natural population of Drosophila melanogaster, individuals that are infected with Wolbachia are less likely to be infected by viruses. By characterising the virome by metagenomic sequencing and then testing individual flies for infection, we found the protective effect of Wolbachia was virus-specific, with the prevalence of infection being up to 15% greater in Wolbachia-free flies. The antiviral effects of Wolbachia may contribute to its extraordinary ecological success, and in nature the symbiont may be an important component of the antiviral defences of insects.
A Household-Based Survey to Understand Factors Influencing Awareness, Attitudes and Knowledge towards Wolbachia-Aedes Technology
19435L. T. Soh, Z. Ong, K. Vasquez, I. Chen, X. Li, W. Niah, C. Panchapakesan, A. Sheldenkar, S. Sim, L. C. Ng and M. O. Lwin, International Journal of Environmental Research and Public Health, 18. 2021-11-15 20:37:00.
In 2016, Singapore introduced the release of male Wolbachia-Aedes mosquitoes to complement vector control efforts and suppress Aedes aegypti mosquitoes in selected study sites. With ongoing expansion of Project Wolbachia-Singapore to cover larger areas, a household-based survey was conducted between July 2019 to February 2020 in two Project Wolbachia study sites using a structured questionnaire, to evaluate current sentiments and assess the need for enhanced public messaging and engagement. The association of factors that influence awareness, attitudes, and knowledge towards the use of Wolbachia-Aedes technology was analysed using Pearson's Chi-square test and binary logistic regression. Of 500 respondents, 74.8% were aware of Project Wolbachia-Singapore. Comparatively, the level of knowledge on Wolbachia-Aedes technology was lower, suggesting knowledge gaps that require enhanced communication and messaging to address misinformation. Longer exposure to the project predicted greater awareness, whereas higher education levels predicted higher knowledge levels. Younger age groups and higher education levels were associated with high acceptance towards the project. High levels of trust and acceptance towards the project were also observed across the population. The public's positive perception of the project is a testament to the effective public communication undertaken to date and will facilitate programme expansion.
High Temperature Cycles Result in Maternal Transmission and Dengue Infection Differences Between Wolbachia Strains in Aedes aegypti
19221M. V. Mancini, T. H. Ant, C. S. Herd, J. Martinez, S. M. Murdochy, D. D. Gingell, E. Mararo, P. C. D. Johnson and S. P. Sinkins, mBio, e0025021. 2021-11-10 21:39:39.
Environmental factors play a crucial role in the population dynamics of arthropod endosymbionts, and therefore in the deployment of Wolbachia symbionts for the control of dengue arboviruses. The potential of Wolbachia to invade, persist, and block virus transmission depends in part on its intracellular density. Several recent studies have highlighted the importance of larval rearing temperature in modulating Wolbachia densities in adults, suggesting that elevated temperatures can severely impact some strains, while having little effect on others. The effect of a replicated tropical heat cycle on Wolbachia density and levels of virus blocking was assessed using Aedes aegypti lines carrying strains wMel and wAlbB, two Wolbachia strains currently used for dengue control. Impacts on intracellular density, maternal transmission fidelity, and dengue inhibition capacity were observed for wMel. In contrast, wAlbB-carrying Ae. aegypti maintained a relatively constant intracellular density at high temperatures and conserved its capacity to inhibit dengue. Following larval heat treatment, wMel showed a degree of density recovery in aging adults, although this was compromised by elevated air temperatures. IMPORTANCE In the past decades, dengue incidence has dramatically increased all over the world. An emerging dengue control strategy utilizes Aedes aegypti mosquitoes artificially transinfected with the bacterial symbiont Wolbachia, with the ultimate aim of replacing wild mosquito populations. However, the rearing temperature of mosquito larvae is known to impact on some Wolbachia strains. In this study, we compared the effects of a temperature cycle mimicking natural breeding sites in tropical climates on two Wolbachia strains, currently used for open field trials. When choosing the Wolbachia strain to be used in a dengue control program it is important to consider the effects of environmental temperatures on invasiveness and virus inhibition. These results underline the significance of understanding the impact of environmental factors on released mosquitoes, in order to ensure the most efficient strategy for dengue control.
Prevalence and molecular characterization of Wolbachia in field-collected Aedes albopictus, Anopheles sinensis, Armigeres subalbatus, Culex pipiens and Cx. tritaeniorhynchus in China
19078Y. Yang, Y. He, G. Zhu, J. Zhang, Z. Gong, S. Huang, G. Lu, Y. Peng, Y. Meng, X. Hao, C. Wang, J. Sun and S. Shang, PLOS Neglected Tropical Diseases, 15:e0009911. 2021-10-29 20:41:21.
Wolbachia are maternally transmitted intracellular bacteria that can naturally and artificially infect arthropods and nematodes. Recently, they were applied to control the spread of mosquito-borne pathogens by causing cytoplasmic incompatibility (CI) between germ cells of females and males. The ability of Wolbachia to induce CI is based on the prevalence and polymorphism of Wolbachia in natural populations of mosquitoes. In this study, we screened the natural infection level and diversity of Wolbachia in field-collected mosquitoes from 25 provinces of China based on partial sequence of Wolbachia surface protein (wsp) gene and multilocus sequence typing (MLST). Among the samples, 2489 mosquitoes were captured from 24 provinces between July and September, 2014 and the remaining 1025 mosquitoes were collected month-by-month in Yangzhou, Jiangsu province between September 2013 and August 2014. Our results showed that the presence of Wolbachia was observed in mosquitoes of Aedes albopictus (97.1%, 331/341), Armigeres subalbatus (95.8%, 481/502), Culex pipiens (87.0%, 1525/1752), Cx. tritaeniorhynchus (17.1%, 14/82), but not Anopheles sinensis (n = 88). Phylogenetic analysis indicated that high polymorphism of wsp and MLST loci was observed in Ae. albopictus mosquitoes, while no or low polymorphisms were in Ar. subalbatus and Cx. pipiens mosquitoes. A total of 12 unique mutations of deduced amino acid were identified in the wsp sequences obtained in this study, including four mutations in Wolbachia supergroup A and eight mutations in supergroup B. This study revealed the prevalence and polymorphism of Wolbachia in mosquitoes in large-scale regions of China and will provide some useful information when performing Wolbachia-based mosquito biocontrol strategies in China.
Wolbachia goes to work in the war on mosquitoes
19076S. Ong, Nature, 598:S32-s34. 2021-10-29 20:37:48.
There are two approaches to tackling dengue with Wolbachia. The first involves releasing only modified male mosquitoes. Since 2015, this strategy has been successfully adopted in Singapore and Guangzhou, China, and in parts of the United States, such as Miami, Texas and California. Because eggs produced from unmodified females that mate with modified males do not hatch, the number of mosquitoes in the community is greatly reduced. The second approach, used by some cities in Vietnam, Indonesia, Malaysia, Brazil and Australia, among others, involves releasing modified mosquitoes of both sexes. The infected females pass the bacteria to their offspring. Over time (several months to years, depending on characteristics of the release site), the modified mosquitoes replace the native population.
A decade of stability for wMel Wolbachia in natural Aedes aegypti populations
19080P. A. Ross, K. L. Robinson, Q. Yang, A. G. Callahan, T. L. Schmidt, J. K. Axford, M. P. Coquilleau, K. M. Staunton, M. Townsend, S. A. Ritchie, M.-J. Lau, X. Gu and A. A. Hoffmann, bioRxiv, 2021.10.27.466190. 2021-10-28 20:41:44.
Mosquitoes carrying Wolbachia endosymbionts are being released in many countries for arbovirus control. The wMel strain of Wolbachia blocks Aedes-borne virus transmission and can spread throughout mosquito populations by inducing cytoplasmic incompatibility. Aedes aegypti mosquitoes carrying wMel were first released into the field in Cairns, Australia, over a decade ago, and with wider releases have resulted in the near elimination of local dengue transmission. The long-term stability of Wolbachia effects is critical for ongoing disease suppression, requiring tracking of phenotypic and genomic changes in Wolbachia infections following releases. We used a combination of field surveys, phenotypic assessments, and Wolbachia genome sequencing to show that wMel has remained stable in its effects for up to a decade in Australian Ae. aegypti populations. Phenotypic comparisons of wMel-infected and uninfected mosquitoes from near-field and long-term laboratory populations suggest limited changes in the effects of wMel on mosquito fitness. Treating mosquitoes with antibiotics used to cure the wMel infection had limited effects on fitness in the next generation, supporting the use of tetracycline for generating uninfected mosquitoes without off-target effects. wMel has a temporally stable within-host density and continues to induce complete cytoplasmic incompatibility. A comparison of wMel genomes from pre-release (2010) and nine years post-release (2020) populations show few genomic differences and little divergence between release locations, consistent with the lack of phenotypic changes. These results indicate that releases of Wolbachia-infected mosquitoes for population replacement are likely to be effective for many years, but ongoing monitoring remains important to track potential evolutionary changes.Competing Interest StatementThe authors have declared no competing interest.
RNA virome diversity and Wolbachia infection in individual Drosophila simulans flies
19073A. S. Ortiz-Baez, M. Shi, A. A. Hoffmann and E. C. Holmes, Journal of General Virology, 102. 2021-10-28 20:29:18.
The endosymbiont bacteria of the genus Wolbachia are associated with multiple mutualistic effects on insect biology, including nutritional and antiviral properties. Members of the genus Wolbachia naturally occur in fly species of the genus Drosophila, providing an operational model host for studying how virome composition may be affected by its presence. Drosophila simulans populations can carry a variety of strains of members of the genus Wolbachia, with the wAu strain associated with strong antiviral protection under experimental conditions. We used D. simulans sampled from the Perth Hills, Western Australia, to investigate the potential virus protective effect of the wAu strain of Wolbachia on individual wild-caught flies. Our data revealed no appreciable variation in virus composition and abundance between individuals infected or uninfected with Wolbachia associated with the presence or absence of wAu. However, it remains unclear whether wAu might affect viral infection and host survival by increasing tolerance rather than inducing complete resistance. These data also provide new insights into the natural virome diversity of D. simulans. Despite the small number of individuals sampled, we identified a repertoire of RNA viruses, including nora virus, galbut virus, thika virus and La Jolla virus, that have been identified in other species of the genus Drosophila. Chaq virus-like sequences associated with galbut virus were also detected. In addition, we identified five novel viruses from the families Reoviridae, Tombusviridae, Mitoviridae and Bunyaviridae. Overall, this study highlights the complex interaction between Wolbachia and RNA virus infections and provides a baseline description of the natural virome of D. simulans.
Positive selection and horizontal gene transfer in the genome of a male-killing Wolbachia
19006T. Hill, R. L. Unckless and J. I. Perlmutter, Molecular Biology and Evolution, 2021-10-18 15:21:59.
Wolbachia are a genus of widespread bacterial endosymbionts in which some strains can hijack or manipulate arthropod host reproduction. Male killing is one such manipulation in which these maternally transmitted bacteria benefit surviving daughters in part by removing competition with the sons for scarce resources. Despite previous findings of interesting genome features of microbial sex ratio distorters, the population genomics of male-killers remain largely uncharacterized. Here, we uncover several unique features of the genome and population genomics of four Arizonan populations of a male-killing Wolbachia strain, wInn, that infects mushroom-feeding Drosophila innubila. We first compared the wInn genome to other closely related Wolbachia genomes of Drosophila hosts in terms of genome content and confirm that the wInn genome is largely similar in overall gene content to the wMel strain infecting D. melanogaster. However, it also contains many unique genes and repetitive genetic elements that indicate lateral gene transfers between wInn and non-Drosophila eukaryotes. We also find that, in line with literature precedent, genes in the Wolbachia prophage and Octomom regions are under positive selection. Of all the genes under positive selection, many also show evidence of recent horizontal transfer among Wolbachia symbiont genomes. These dynamics of selection and horizontal gene transfer across the genomes of several Wolbachia strains and diverse host species may be important underlying factors in Wolbachia’s success as a male-killer of divergent host species.
Novel Symbiotic Genome-Scale Model Reveals Wolbachia’s Arboviral Pathogen Blocking Mechanism in Aedes aegypti
18936N. E. Jiménez, Z. P. Gerdtzen, Á. Olivera-Nappa, J. C. Salgado and C. Conca, mBio, e0156321. 2021-10-13 20:29:16.
Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of Wolbachia as an approach for disease control has motivated new research related to the characterization of the mechanisms that underlie its pathogen-blocking properties. In this work, we propose a new approach for studying the metabolic interactions between Aedes aegypti and Wolbachia using genome-scale models, finding that pathogen blocking is mainly influenced by competition for the resources required for Wolbachia and viral replication.
Structural and mechanistic insights into the complexes formed by Wolbachia cytoplasmic incompatibility factors
18908Y. Xiao, H. Chen, H. Wang, M. Zhang, X. Chen, J. M. Berk, L. Zhang, Y. Wei, W. Li, W. Cui, F. Wang, Q. Wang, C. Cui, T. Li, C. Chen, S. Ye, L. Zhang, X. Ji, J. Huang, W. Wang, Z. Wang, M. Hochstrasser and H. Yang, Proceedings of the National Academy of Sciences, 118. 2021-10-09 14:35:56.
Wolbachia bacteria, inherited through the female germ line, infect a large fraction of arthropod species. Many Wolbachia strains manipulate host reproduction, most commonly through cytoplasmic incompatibility (CI). CI, a conditional male sterility, results when Wolbachia-infected male insects mate with uninfected females; viability is restored if the female is similarly infected (called "rescue"). CI is used to help control mosquito-borne viruses such as dengue and Zika, but its mechanisms remain unknown. The coexpressed CI factors CifA and CifB form stable complexes in vitro, but the timing and function of this interaction in the insect are unresolved. CifA expression in the female germ line is sufficient for rescue. We report high-resolution structures of a CI-factor complex, CinA-CinB, which utilizes a unique binding mode between the CinA rescue factor and the CinB nuclease; the structures were validated by biochemical and yeast growth analyses. Importantly, transgenic expression in Drosophila of a nonbinding CinA mutant, designed based on the CinA-CinB structure, suggests CinA expressed in females must bind CinB imported by sperm in order to rescue embryonic viability. Binding between cognate factors is conserved in an enzymatically distinct CI system, CidA-CidB, suggesting universal features in Wolbachia CI induction and rescue.
A single mutation weakens symbiont-induced reproductive manipulation through reductions in deubiquitylation efficiency
18742J. F. Beckmann, K. Van Vaerenberghe, D. E. Akwa and B. S. Cooper, Proceedings of the National Academy of Sciences, 118:e2113271118. 2021-09-21 14:01:04.
We show that a single naturally observed mutation weakens CI by reducing deubiquitylation. These discoveries help elucidate the molecular basis of symbiont-induced reproductive manipulations.Animals interact with microbes that affect their performance and fitness, including endosymbionts that reside inside their cells. Maternally transmitted Wolbachia bacteria are the most common known endosymbionts, in large part because of their manipulation of host reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) that reduces host embryonic viability when Wolbachia-modified sperm fertilize uninfected eggs. Operons termed cifs control CI, and a single factor (cifA) rescues it, providing Wolbachia-infected females a fitness advantage. Despite CI’s prevalence in nature, theory indicates that natural selection does not act to maintain CI, which varies widely in strength. Here, we investigate the genetic and functional basis of CI-strength variation observed among sister Wolbachia that infect Drosophila melanogaster subgroup hosts. We cloned, Sanger sequenced, and expressed cif repertoires from weak CI–causing wYak in Drosophila yakuba, revealing mutations suspected to weaken CI relative to model wMel in D. melanogaster. A single valine-to-leucine mutation within the deubiquitylating (DUB) domain of the wYak cifB homolog (cidB) ablates a CI-like phenotype in yeast. The same mutation reduces both DUB efficiency in vitro and transgenic CI strength in the fly, each by about twofold. Our results map hypomorphic transgenic CI to reduced DUB activity and indicate that deubiquitylation is central to CI induction in cid systems. We also characterize effects of other genetic variation distinguishing wMel-like cifs. Importantly, CI strength determines Wolbachia prevalence in natural systems and directly influences the efficacy of Wolbachia biocontrol strategies in transinfected mosquito systems. These approaches rely on strong CI to reduce human disease.All study data are included in the article and/or supporting information.
Discrete dynamical models on Wolbachia infection frequency in mosquito populations with biased release ratios
18717Y. Shi and B. Zheng, Journal of Biological Dynamics, 2021-09-18 14:11:29.
We develop two discrete models to study how supplemental releases affect the Wolbachia spreading dynamics in cage mosquito populations. The first model focuses on the case when only infected males are released at each generation. This release strategy has been proved to be capable of speeding up the Wolbachia persistence by suppressing the compatible matings between uninfected individuals. The second model targets the case when only infected females are released at each generation. For both models, detailed model formulation, enumeration of the positive equilibria and their stability analysis are provided. Theoretical results show that the two models can generate bistable dynamics when there are three positive equilibrium points, semi-stable dynamics for the case of two positive equilibrium points. And when the positive equilibrium point is unique, it is globally asymptotically stable. Some numerical simulations are offered to get helpful implications on the design of the release strategy.
Symbiotic Interactions Between Mosquitoes and Mosquito Viruses
18715M. Altinli, E. Schnettler and M. Sicard, Front Cell Infect Microbiol, 11:694020. 2021-09-17 14:06:45.
Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.
Two newly introduced Wolbachia endosymbionts induce cell host differences in competitiveness and metabolic responses
18510T. P. Li, S. S. Zha, C. Y. Zhou, X. Xia, A. A. Hoffmann and X. Y. Hong, Appl Environ Microbiol, Aem0147921. 2021-09-09 14:34:33.
Wolbachia endosymbionts can induce multiple reproductive manipulations in their hosts, with cytoplasmic incompatibility (CI) being one of the most common manipulations. The important agricultural pests, white-backed planthopper (Sogatella furcifera) and brown planthopper (Nilaparvata lugens), are usually infected with CI-inducing Wolbachia wFur and non-CI-inducing Wolbachia wLug, respectively. The biological effects of these infections when present in a host cell are unknown. Here, we introduced the two Wolbachia strains into an Aedes albopictus cell line to stably establish a wFur-infected cell line (WFI) and a wLug-infected cell line (WLI). In a mixed culture, WFI cells were completely replaced by WLI cells, pointing to a stronger competitiveness of the WLI cell line. We found that infection by both Wolbachia strains reduced cell growth rates, but WLI had a faster cell growth rate than WFI, and this difference in cell growth rate combined with possible Wolbachia differences in diffusivity may have affected cell competitiveness. By examining gene expression and metabolites in the two lines, we found that some genes and key metabolites responded to differences in cell competitiveness. These results point to potential mechanisms that could contribute to the relative performance of hosts infected by these strains and also highlight the substantial impact of a non-CI Wolbachia on metabolism, which may in turn influence fitness of its native host. IMPORTANCE Wolbachia transinfection in insects can be used to suppress pests and block virus transmission. We stably introduced two Wolbachia strains from rice planthoppers into cell lines of an important arbovirus mosquito vector, Aedes albopictus. The competitiveness of host cells from the lines infected by the two Wolbachia strains was different, as were metabolic responses of the cell lines. These results suggest potential metabolic effects of Wolbachia on native hosts which could be exploited when they are transinfected into novel hosts for pest control.
Persistent Spodoptera frugiperda rhabdovirus infection in Sf9 cells is not restricted by Wolbachia wMelPop-CLA and wAlbB strains and is targeted by the RNAi machinery
18362R. Parry, H. de Malmanche and S. Asgari, Virology, 563:82-87. 2021-09-08 14:28:58.
The endosymbiotic bacterium Wolbachia pipientis confers RNA virus refractoriness in Drosophila and Aedes mosquitoes. Questions remain about the Wolbachia-virus restriction phenotype and how extensive this phenomenon may be within other arthropods. Here, we generated two Spodoptera frugiperda cell lines stably transinfected with two strains of Wolbachia, wAlbB and wMelPop-CLA. Despite the high density of Wolbachia in stably infected Sf9 cells, RT-PCR indicated the presence of the negative-sense RNA virus Spodoptera frugiperda rhabdovirus (SfRV) in Wolbachia-infected and uninfected cell lines. No differences in the replication of SfRV between Sf9 and Wolbachia-infected cells was found. RNA-Seq analysis of the parental Sf9 cells supported SfRV's presence in these cells with abundant 20 nt virus-derived small RNAs indicating active replication of SfRV in these cells. Overall, this study supports a growing body of evidence that Wolbachia does not restrict negative-sense RNA viruses and generates an in vitro model to examine Lepidoptera-Wolbachia virus interactions.
Wolbachia-Conferred Antiviral Protection Is Determined by Developmental Temperature
18357E. Chrostek, N. Martins, M. S. Marialva and L. Teixeira, mBio, e0292320. 2021-09-08 14:13:12.
Overall, we show that Wolbachia-conferred antiviral protection is temperature dependent, being present or absent depending on the environmental conditions. This interaction likely impacts Wolbachia-host interactions in nature and, as a result, frequencies of host and symbionts in different climates. Dependence of Wolbachia-mediated pathogen blocking on developmental temperature could be used to dissect the mechanistic bases of protection and influence the deployment of Wolbachia to prevent transmission of arboviruses. IMPORTANCE Insects are often infected with beneficial intracellular bacteria. The bacterium Wolbachia is extremely common in insects and can protect them from pathogenic viruses. This effect is being used to prevent transmission of dengue and Zika viruses by Wolbachia-infected mosquitoes. To understand the biology of insects in the wild, we need to discover which factors affect Wolbachia-conferred antiviral protection. Here, we show that the temperature at which insects develop from eggs to adults can determine the presence or absence of antiviral protection. The environment, therefore, strongly influences this insect-bacterium interaction. Our work may help to provide insights into the mechanism of viral blocking by Wolbachia, deepen our understanding of the geographical distribution of host and symbiont, and incentivize further research on the temperature dependence of Wolbachia-conferred protection for control of mosquito-borne disease.
Diverse wMel variants of Wolbachia pipientis differentially rescue fertility and cytological defects of the bag of marbles partial loss of function mutation in Drosophila melanogaster
18817J. E. Bubnell, P. Fernandez-Begne, C. K. S. Ulbing and C. F. Aquadro, G3 Genes|Genomes|Genetics, 2021-09-07 15:29:22.
In Drosophila melanogaster, the maternally inherited endosymbiont Wolbachia pipientis interacts with germline stem cell genes during oogenesis. One such gene, bag of marbles (bam) is the key switch for differentiation and also shows signals of adaptive evolution for protein diversification. These observations have led us to hypothesize that W. pipientis could be driving the adaptive evolution of bam for control of oogenesis. To test this hypothesis, we must understand the specificity of the genetic interaction between bam and W. pipientis. Previously, we documented that the W. pipientis variant, wMel, rescued the fertility of the bamBW hypomorphic mutant as a transheterozygote over a bam null. However, bamBW was generated more than 20 years ago in an uncontrolled genetic background and maintained over a balancer chromosome. Consequently, the chromosome carrying bamBW accumulated mutations that have prevented controlled experiments to further assess the interaction. Here, we used CRISPR/Cas9 to engineer the same single amino acid bam hypomorphic mutation (bamL255F) and a new bam null disruption mutation into the w1118 isogenic background. We assess the fertility of wildtype bam, bamL255F/bamnull hypomorphic, and bamL255F/bamL255F mutant females, each infected individually with 10 W. pipientis wMel variants representing three phylogenetic clades. Overall, we find that all of the W. pipientis variants tested here rescue bam hypomorphic fertility defects with wMelCS-like variants exhibiting the strongest rescue effects. In addition, these variants did not increase wildtype bam female fertility. Therefore, both bam and W. pipientis interact in genotype-specific ways to modulate female fertility, a critical fitness phenotype.
Assessment of fitness and vector competence of a New Caledonia wMel Aedes aegypti strain before field-release
18360N. Pocquet, O. O’Connor, H. A. Flores, J. Tutagata, M. Pol, D. J. Hooker, C. Inizan, S. Russet, J. M. Duyvestyn, E. C. Pacidônio, D. Girault, D. da Silva Gonçalves, M. Minier, F. Touzain, E. Chalus, K. Lucien, F. Cheilan, T. Derycke, S. Laumond, C. P. Sim, PLOS Neglected Tropical Diseases, 15:e0009752. 2021-09-07 14:13:26.
Dengue represents a risk for almost half of the world’s population, especially throughout the tropics. In New Caledonia, dengue outbreaks have become more frequent in the past decade along with the recent circulation of chikungunya and Zika viruses. The opportunity to use the biocontrol method involving the release of Wolbachia-infected Ae. aegypti mosquitoes has been investigated as an alternative solution to the traditional control methods, like elimination of larval habitats and pyrethroid insecticide application to kill adults, which are becoming insufficient. A local strain of Ae. aegypti carrying Wolbachia (NC-wMel) has been generated and tested to evaluate its pathogen blocking capacity for the four dengue virus serotypes as well as chikungunya and Zika viruses. The fitness of NC-wMel strain has also been assessed to estimate its ability to compete with the wild-type strain in the field. Noumea city, where a third of the population of New Caledonia resides, has been chosen as the first site to implement the method in New Caledonia. As Ae. aegypti is the only proven vector in New Caledonia, we expect a significant impact on dengue outbreaks occurring in Noumea as soon as a high frequency of NC-wMel is established in the population.
wMel Wolbachia genome remains stable after 7 years in Australian Aedes aegypti field populations
18281K. R. Dainty, J. Hawkey, L. M. Judd, E. C. Pacidônio, J. M. Duyvestyn, D. S. Gonçalves, S. Y. Lin, T. B. O'Donnell, S. L. O'Neill, C. P. Simmons, K. E. Holt and H. A. Flores, Microbial Genomics, 7. 2021-09-02 14:23:53.
Infection of wMel Wolbachia in Aedes aegypti imparts two signature features that enable its application for biocontrol of dengue. First, the susceptibility of mosquitoes to viruses such as dengue and Zika is reduced. Second, a reproductive manipulation is caused that enables wMel introgression into wild-type mosquito populations. The long-term success of this method relies, in part, on evolution of the wMel genome not compromising the critical features that make it an attractive biocontrol tool. This study compared the wMel Wolbachia genome at the time of initial releases and 1-7 years post-release in Cairns, Australia. Our results show the wMel genome remains highly conserved up to 7 years post-release in gene sequence, content, synteny and structure. This work suggests the wMel genome is stable in its new mosquito host and, therefore, provides reassurance on the potential for wMel to deliver long-term public-health impacts.
Millions of Lab-Grown Mosquitoes Are Being Released in Guangzhou
18219F. Yiying, Sixth Tone, 2021-08-25 15:26:45.
Guangzhou is releasing millions of lab-engineered mosquitoes every day to neuter and prevent preexisting mosquitoes in the environment from spreading vector-borne diseases, local television station reported Saturday.The Guangzhou Wolbaki Biotech Co., Ltd., in partnership with the city’s disease control and prevention bureau, releases about five million lab-grown male mosquitoes daily, which only mate with aedes albopictus mosquitoes to stop them from reproducing disease-carrying offspring, according to the media report. Only female aedes albopictus, also known as tiger mosquitoes, prey on people, potentially transmitting the viruses that cause dengue and chikungunya, among other illnesses.The biotech company’s “mosquito factory” in Guangzhou — where dengue fever is a public health concern — breeds mosquitoes to produce offspring carrying the Wolbachia bacteria, which is commonly found in insects and not harmful to humans, before releasing them to the environment. When mosquitoes carrying Wolbachia mate with aedes albopictus, it reduces the replication of the viruses they carry, making them less likely to transmit it to humans.
Sex separation of Aedes spp. mosquitoes for sterile insect technique application: a review
17905B. M. Moran-Aceves, C. F. Marina, A. Dor, P. Liedo and J. Toledo, Entomologia Experimentalis Et Applicata, 10. 2021-07-24 15:04:30.
Separation of the sexes is necessary for the application of the sterile insect technique (SIT) in mosquitoes due to the hematophagous habits and disease vector activity of the females. In this review we analyze the history, current status, and future perspectives for the development of genetic sexing strains (GSS) of Aedes mosquitoes (Diptera: Culicidae). Various genetic control methods for mosquitoes are reviewed, as are their need for sex-separation methods. We focus on areas of opportunity where GSS developed with classical genetic methods can be used. Regulatory restrictions and social acceptance of various control methods are analyzed. We conclude that the development of GSS by classical methods represents the most viable option for separation of the sexes and the application of large-scale SIT programs within an area-wide integrated vector management (AW-IVM) approach.
Wolbachia as translational science: controlling mosquito-borne pathogens
17799E. P. Caragata, H. L. C. Dutra, P. H. F. Sucupira, A. G. A. Ferreira and L. A. Moreira, Trends in Parasitology, 2021-07-22 20:54:55.
In this review we examine how exploiting the Wolbachia?mosquito relationship has become an increasingly popular strategy for controlling arbovirus transmission. Field deployments of Wolbachia-infected mosquitoes have led to significant decreases in dengue virus incidence via high levels of mosquito population suppression and replacement, emphasizing the success of Wolbachia approaches. Here, we examine how improved knowledge of Wolbachia?host interactions has provided key insight into the mechanisms of the essential phenotypes of pathogen blocking and cytoplasmic incompatibility. And we discuss recent studies demonstrating that extrinsic factors, such as ambient temperature, can modulate Wolbachia density and maternal transmission. Finally, we assess the prospects of using Wolbachia to control other vectors and agricultural pest species.
Combating mosquito-borne diseases using genetic control technologies
17735G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari, Nature Communications, 12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.
A wAlbB Wolbachia< transinfection displays stable phenotypic effects across divergent Aedes aegypti mosquito backgrounds
17592P. A. Ross, X. Gu, K. L. Robinson, Q. Yang, E. Cottingham, Y. Zhang, H. L. Yeap, X. Xu, N. M. Endersby-Harshman and A. A. Hoffmann, bioRxiv, 2021.06.25.450002. 2021-06-26 14:00:37.
Aedes mosquitoes harboring intracellular Wolbachia bacteria are being released in arbovirus and mosquito control programs. With releases taking place around the world, understanding the contribution of host variation to Wolbachia phenotype is crucial. We generated a Wolbachia transinfection (wAlbBQ) in Aedes aegypti and performed backcrossing to introduce the infection into Australian or Malaysian nuclear backgrounds. Whole Wolbachia genome sequencing shows that the wAlbBQ transinfection is near-identical to the reference wAlbB genome, suggesting few changes since the infection was first introduced to Ae. aegypti over 15 years ago. However, these sequences were distinct from other available wAlbB genome sequences, highlighting the potential diversity of wAlbB in natural Ae. albopictus populations. Phenotypic comparisons demonstrate effects of wAlbB infection on egg hatch and nuclear background on fecundity and body size, but no interactions between wAlbB infection and nuclear background for any trait. The wAlbB infection was stable at high temperatures and showed perfect maternal transmission and cytoplasmic incompatibility regardless of host background. Our results demonstrate the stability of wAlbB across host backgrounds and point to its long-term effectiveness for controlling arbovirus transmission and mosquito populations.Competing Interest StatementThe authors have declared no competing interest.
Manipulated Mosquitoes Cut Dengue by 77%
17513T. Hayes, Healthcare Packaging, 2021-06-22 14:34:21.
Dengue, a mosquito-borne viral disease, wasn’t that common 50 years ago. In fact, only nine countries had severe outbreaks. But since then, it’s been on a steady incline to the point that there are now 400 million infections a year that contribute to 22,000 deaths. Thankfully, we have the World Mosquito Programme, a group that’s fighting the tropical mosquito disease head-on with genetically modified mosquitoes. The insects are infected with Wolbachia, a bacteria that inhibits viruses’ ability to live inside the insects, and also controls reproduction so that offspring are also infected with the bacteria. The result is a new population of insects that can’t transmit viruses like dengue, yellow fever and Zika. The study in Indonesia included 8,000 people, and concluded with protective efficacy of 77.1%.
Wolbachia-mediated sterility suppresses Aedes aegypti populations in the urban tropics
19443Project Wolbachia-Singapore Consortium, medRxiv, 2021-06-17 21:07:26.
Incompatible insect technique (IIT) via releases of male Wolbachiainfected mosquitoes is a promising tool for dengue control. In a three-year trial in Singaporean high-rise housing estates, we demonstrated that Wolbachia-based IIT dramatically reduces both wildtype Aedes aegypti populations [reductions of 92.7% (95% CI: 84.7%–95.8%) and 98.3% (97.7%–99.8%)] and dengue incidence [reductions of 71% (43%-87%) to 88% (57%-99%)] in the targeted areas. The study highlights the need to ensure adequate vertical distribution of released males in high-rise buildings, address immigration of wildtype females from neighboring areas, and prevent and mitigate stable establishment of Wolbachia in field mosquito populations. Our results demonstrate the potential of Wolbachia-based IIT (supplemented with irradiation, in Singapore’s context) for strengthening dengue control in tropical cities, where dengue burden is the greatest.
Dengue fever: Upstaged but not outmatched by COVID-19
17490C. E. Baclig, INQUIRER.NET, 2021-06-17 15:17:30.
Science has made gains in the war on dengue and other diseases that mosquitoes carry, like malaria.One of these is the World Mosquito Program (WMP), a non-profit initiative that aims to protect the global community from mosquito-borne viral diseases, by deploying a natural bacteria, called Wolbachia. On its website, WMP said its scientists had discovered that Aedis aegypti mosquitoes carry Wolbachia, a bacteria which competes with viruses like dengue, zika, chikungunya, and the virus that causes yellow fever. Wolbachia, WMP said, was found to make it difficult for viruses to reproduce inside mosquitoes. Mosquitoes carrying Wolbachia, WPS said, “are much less likely to spread viruses from person to person.” Wolbachia is found in 60 percent of insects but is not normally carried by Aedis aegypti mosquitoes. So scientists injected the bacteria into mosquito eggs. Once these hatches and send off grown mosquitoes, they are released to breed with local mosquito populations.
Dengue Infections Can Be Sharply Reduced With Wolbachia Bacteria
17453J. Stone, Medscape, 2021-06-14 17:25:12.
A modestly titled new study released in the New England Journal of Medicine belies the extraordinary 77% protective efficacy reported for preventing dengue infections with Wolbachia-infected Aedes aegypti mosquitoes. A cluster-randomized clinical trial, the AWED ("Applying Wolbachia to Eliminate Dengue") study was conducted in Yogyakarta, Indonesia and led by professors Adi Utarini, MD, PhD, of Gadjah Mada University and Cameron Simmons, PhD, the World Mosquito Program's Oceana director, in partnership with the Tahija Foundation and Monash University.
Making mosquitoes to fight mosquitoes to prevent dengue
17484A. George, Times of India, 2021-06-14 15:04:01.
In 2017, Delhi Chief Minister Arvind Kejriwal tweeted that the national capitl needed to be made mosquito-free. The same year, his Kerala counterpart, Pinaray Vijayan, called a three-day state-wide cleanliness drive as hospitals filled with genue patients.
Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes
17504T. Walker, S. Quek, C. L. Jeffries, J. Bandibabone, V. Dhokiya, R. Bamou, M. Kristan, L. A. Messenger, A. Gidley, E. A. Hornett, E. R. Anderson, C. Cansado-Utrilla, S. Hegde, C. Bantuzeko, J. C. Stevenson, N. F. Lobo, S. C. Wagstaff, C. A. Nkondjio, S. R., Current Biology, 31:2310. 2021-06-14 13:55:55.
Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An. gambiae complex, the primary vectors of Plasmodium malaria in Sub-Saharan Africa, Wolbachia DNA sequences at low density and infection frequencies have been detected. As the majority of studies have used highly sensitive nested PCR as the only method of detection, more robust evidence is required to determine whether Wolbachia strains are established as endosymbionts in Anopheles species. Here, we describe high-density Wolbachia infections in geographically diverse populations of An. moucheti and An. demeilloni. Fluorescent in situ hybridization localized a heavy infection in the ovaries of An. moucheti, and maternal transmission was observed. Genome sequencing of both Wolbachia strains obtained genome depths and coverages comparable to those of other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present, indicating that these strains possess the capacity to induce the cytoplasmic incompatibility phenotype, which allows Wolbachia to spread through host populations. These strains should be further investigated as candidates for use in Wolbachia biocontrol strategies in Anopheles aiming to reduce the transmission of malaria.
Using Wolbachia to Eliminate Dengue: Will the Virus Fight Back?
18270M. Edenborough Kathryn, A. Flores Heather, P. Simmons Cameron, E. Fraser Johanna and C. Pierson Ted, Journal of Virology, 95:e02203-20. 2021-06-10 14:06:11.
Recent fieldtrials havedemonstratedthatdengue incidence can besubstantially reduced by introgressing strains of the endosymbiotic bacterium Wolbachia into Aedes aegypti mosquito populations. This strategy relies on Wolbachia reducing the susceptibility of Ae. aegypti to disseminated infection by positive-sense RNA viruses like dengue. However, RNA viruses are well known to adapt to antiviral pressures. Here, we review the viral infection stages where selection for Wolbachia-resistant virus variants could occur. We also consider the genetic constraints imposed on viruses that alternate between vertebrate and invertebrate hosts, and the likely selection pressures to which dengue virus might adapt in order to be effectively transmitted by Ae. aegypti that carry Wolbachia. While there are hurdles to dengue viruses developing resistance to Wolbachia, we suggest that long-term surveillance for resistant viruses should be an integral component of Wolbachia-introgression biocontrol programs.
Dengue Fever Cut Down by 77% With Groundbreaking Bacteria-Armed Mosquitoes
17322M. Davis, The Science Times, 2021-06-10 12:02:22.
Scientists found that dengue fever cases have decreased by 77% in a groundbreaking trial that took place in Yogyakarta City, Indonesia. They used Wolbachia-infected mosquitoes that reduced their ability to spread the dengue fever. The team at the World Mosquito Program said that this could be a solution to dengue fever that is prevalent around the world. Dr. Katie Anders, one of the researchers, described the trial of using Wolbachia-infected mosquitoes in Indonesia as a "naturally miraculous" solution. Wolbachia is a virus-fighting bacteria that has been approved since 2017 by the Environmental Protection Agency (EPA) for use in the United States. Other interventions, like genetically modified mosquitoes, are also used to combat dengue fever and other diseases caused by mosquitoes. According to BBC News, Wolbachia does not harm the mosquito, but it will only be stored in the same parts of the mosquito's body where the dengue virus is kept. It competes for the resources, preventing the dengue virus to replicate, and therefore the mosquito is less likely to cause the infection when it bites. Moreover, Wolbachia bacteria can also manipulate and alter the fertility of their hosts. They make sure that they are passed on to the next generation of mosquitoes, which means they are established and should stick around for a long time to continue their protective abilities against dengue fever.
Mosquito ‘bacteria hack’ nearly eliminates dengue fever and could save millions of lives
17316A. Wilkins, METRO, 2021-06-10 11:50:12.
Mosquitoes infected with a ‘miraculous’ bacteria have been shown to reduce dengue fever cases by 77%, in a groundbreaking new study. Scientists released mosquitoes infected with ‘Wolbachia’ bacteria into the Indonesian city of Yogyakarta – but only in certain zones. In the zones where the modified mosquitoes had been released, cases of dengue fell by 77% and hospitalisations dropped by 86%. The results of the study, carried out by the World Mosquito Programme (WMP), were ‘better than we could have hoped for’, according to researcher Dr. Katie Anders. Cases of dengue fever, a virus that can cause muscle and bone pain, and death, have risen rapidly in the past decades – there are an estimated 400 million cases a year. The Wolbachia bacteria used in the trial were chosen because it hides in the same parts of a mosquito’s body that dengue virus hides in. A bacteria that is benign to humans, the Wolbachia then competes for resources with the dengue virus, which makes it less likely for the mosquito to cause a dengue infection when it bites a human.
‘Miraculous’ mosquito hack cuts dengue by 77%
17311J. Gallagher, BBC, 2021-06-10 11:38:57.
Dengue fever cases have been cut by 77% in a "groundbreaking" trial that manipulates the mosquitoes that spread it, say scientists. They used mosquitoes infected with "miraculous" bacteria that reduce the insect's ability to spread dengue. The trial took place in Yogyakarta city, Indonesia, and is being expanded in the hope of eradicating the virus. The World Mosquito Programme team says it could be a solution to a virus that has gone around the world. Few people had heard of dengue 50 years ago, but it has been a relentless slow-burning pandemic and cases have increased dramatically. In 1970, only nine countries had faced severe dengue outbreaks, now there are up to 400 million infections a year. Dengue is commonly known as "break-bone fever" because it causes severe pain in muscles and bones and explosive outbreaks can overwhelm hospitals.
Modified mosquitoes reduce dengue cases by 77% in Indonesia experiment
17309M. Fox, CNN, 2021-06-10 11:32:59.
An experiment to infect mosquitoes with bacteria that stop them from transmitting viruses appears to have helped reduced the spread of deadly dengue virus in Indonesia, researchers reported Wednesday. The modified mosquitoes thrived for three years, and cases of dengue were reduced by 77% in areas where they were introduced, the researchers reported in the New England Journal of Medicine. The mosquitoes are infected with bacteria called Wolbachia, which not only interfere with the ability of viruses to live in the bodies of the insects, but which also control reproduction so that the mosquitoes only have Wolbachia-infected offspring. The result is a growing population of insects that don't pass on viruses such as dengue, yellow fever and Zika. The study involved more than 8,000 people, about half of whom lived in areas where the modified Aedes aegypti mosquitoes had been living and breeding.
Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue
17300A. Utarini, C. Indriani, R. A. Ahmad, W. Tantowijoyo, E. Arguni, M. R. Ansari, E. Supriyati, D. S. Wardana, Y. Meitika, I. Ernesia, I. Nurhayati, E. Prabowo, B. Andari, B. R. Green, L. Hodgson, Z. Cutcher, E. Rancès, P. A. Ryan, S. L. O’Neill, S. M. Dufau, New England Journal of Medicine, 384:2177-2186. 2021-06-10 11:05:41.
BACKGROUND Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection. METHODS We conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype. RESULTS After successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P=0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3).
A Pivotal Mosquito Experiment Could Not Have Gone Better
17294E. Yong, The Atlantic, 2021-06-10 10:50:58.
The World Mosquito Program (WMP), a nonprofit that pioneered this technique, had run small pilot studies in Australia that suggested it could work. Utarini, who co-leads WMP Yogyakarta, has now shown conclusively that it does. Her team released Wolbachia-carrying mosquitoes in parts of Yogyakarta as part of a randomized controlled trial. The results, which were unveiled last year and have now been published, showed that Wolbachia rapidly spread among the local mosquitoes, and reduced the incidence of dengue by 77 percent. “That provides the gold standard of evidence that Wolbachia is a highly effective intervention against dengue,” says Oliver Brady, a dengue expert at the London School of Hygiene and Tropical Medicine, who was not involved in the study. “It has the potential to revolutionize mosquito control.” The trial’s results were so encouraging that the researchers have since released Wolbachia-carrying mosquitoes over all of central Yogyakarta—a 32-square-kilometer zone that’s home to more than 400,000 people. They’re now expanding into the densest surrounding provinces, aiming to protect 4 million people by the end of 2022. If they succeed, they should be able to prevent more than 10,000 dengue infections every year, Katherine Anders of the WMP told me. And the team is optimistic enough that it’s daring to think about an even grander goal: eliminating dengue from the city altogether.
Mosquitoes armed with virus-fighting bacteria sharply curb dengue infections, hospitalizations
17319K. Servick, Science, 2021-06-09 11:55:26.
A strategy for fighting dengue fever with bacteria-armed mosquitoes has passed its most rigorous test yet: a large, randomized, controlled trial. Researchers reported today dramatic reductions in rates of dengue infection and hospitalization in areas of an Indonesian city where the disease-fighting mosquitoes were released. The team expects the World Health Organization (WHO) to formally recommend the approach for broader use. The findings are a “breakthrough” that brings the approach “much closer to … being an official strategy to control dengue,” says Ewa Chrostek, an infection biologist at the University of Liverpool who was not involved with the work. WHO estimates there are 100 million to 400 million infections per year with dengue, which can cause high fever and severe joint pain. The bacterium Wolbachia pipientis naturally inhabits many insects, though not Aedes aegypti mosquitoes, the main transmitter of dengue virus. In A. aegypti cells, the bacterium can block viruses, including dengue, from replicating, making the insects less likely to spread disease when they bite humans. That has made the microbe a promising strategy for fighting dengue. In tropical regions, where mosquito-borne viruses are common, other strategies such as insecticides have failed to fully control the disease.
Study demonstrates ‘exciting potential’ of Wolbachia-infected mosquitoes to control dengue
17313G. Gallagher, Healio, 2021-06-09 11:43:08.
The release of Wolbachia-infected mosquitoes led to a 77% reduction in the incidence of symptomatic dengue in an Indonesian city, according to researchers, who said the same approach could be used to fight other mosquito-borne diseases. The study tested a strain of Wolbachia pipientis called wMel that makes Aedes aegypti mosquitoes less susceptible to dengue virus infection. Wolbachia pipientis occurs naturally in many insects but not A. aegypti, the primary vector of dengue, according to Adi Utarini, PhD, MPH, MSc, and colleagues from the nonprofit World Mosquito Program, which has been releasing Wolbachia-infected mosquitoes in the wild since 2011. A study in Indonesia demonstrated the potential of a natural intervention to significantly reduce the incidence of dengue, the world’s most prevalent mosquito-borne disease. “Wolbachia facilitates its own population introgression by manipulating reproductive outcomes between wild-type and Wolbachia-infected mosquitoes: the only viable mating outcomes are those in which the progeny are infected with Wolbachia,” they wrote in the new report, which was published Wednesday in The New England Journal of Medicine.
Vector control: Discovery of Wolbachia in malaria vectors
17554P. A. Ross and A. A. Hoffmann, Current Biology, 31:R738-R740. 2021-06-07 14:28:04.
Wolbachia bacteria are being widely released for suppression of dengue transmitted by Aedes mosquitoes. Walker, Quek, Jeffries and colleagues present robust evidence for natural Wolbachia infections in malaria-vectoring Anopheles mosquitoes, paving the way for new Wolbachia-based intervention
Living in the endosymbiotic world of Wolbachia: A centennial review
17794R. Kaur, J. D. Shropshire, K. L. Cross, B. Leigh, A. J. Mansueto, V. Stewart, S. R. Bordenstein and S. R. Bordenstein, Cell Host and Microbe, 29:879-893. 2021-05-03 20:31:30.
The most widespread intracellular bacteria in the animal kingdom are maternally inherited endosymbionts of the genus Wolbachia. Their prevalence in arthropods and nematodes worldwide and stunning arsenal of parasitic and mutualistic adaptations make these bacteria a biological archetype for basic studies of symbiosis and applied outcomes for curbing human and agricultural diseases. Here, we conduct a summative, centennial analysis of living in the Wolbachia world. We synthesize literature on Wolbachia's host range, phylogenetic diversity, genomics, cell biology, and applications to filarial, arboviral, and agricultural diseases. We also review the mobilome of Wolbachia including phage WO and its essentiality to hallmark reproductive phenotypes in arthropods. Finally, the Wolbachia system is an exemplar for discovery-based science education using biodiversity, biotechnology, and bioinformatics lessons. As we approach a century of Wolbachia research, the interdisciplinary science of this symbiosis stands as a model for consolidating and teaching the integrative rules of endosymbiotic life.
Mechanistically comparing reproductive manipulations caused by selfish chromosomes and bacterial symbionts
16958E. Dalla Benetta, O. S. Akbari and P. M. Ferree, Heredity, 126:707-716. 2021-05-01 14:52:23.
Insects naturally harbor a broad range of selfish agents that can manipulate their reproduction and development, often leading to host sex ratio distortion. Such effects directly benefit the spread of the selfish agents. These agents include two broad groups: bacterial symbionts and selfish chromosomes. Recent studies have made steady progress in uncovering the cellular targets of these agents and their effector genes. Here we highlight what is known about the targeted developmental processes, developmental timing, and effector genes expressed by several selfish agents. It is now becoming apparent that: (1) the genetic toolkits used by these agents to induce a given reproductive manipulation are simple, (2) these agents target sex-specific cellular processes very early in development, and (3) in some cases, similar processes are targeted. Knowledge of the molecular underpinnings of these systems will help to solve long-standing puzzles and provide new tools for controlling insect pests.
Modeling and analysis of the implementation of the Wolbachia incompatible and sterile insect technique for mosquito population suppression.
17098B. Zheng, J. S. Yu and J. Li, Siam Journal on Applied Mathematics, 81:718-740. 2021-04-29 13:06:06.
Mathematical analysis may offer guidance in designing effective mass release strategies for the area-wide application of this Wolbachia incompatible and sterile insect technique in the future. The two most crucial concerns in designing release strategies are how often and in what amount should Wolbachia-infected mosquitoes be released in order to guarantee population suppression. Motivated by the experimental data from the Guangzhou mosquito factory and the release strategy implemented on two islands, we formulate and analyze a mosquito population suppression model considering the situation for the release period T less than the sexual lifespan of Wolbachia-infected males. We define release amount thresholds g(1)* and g(2)* with g(1)* < g(2)*. When the release amount c satisfies c >= g(2)*, population suppression is always achievable, as is mathematically manifested by the global asymptotic stability of the origin. However, when c is an element of (0, g(1)*], we find that suppression can be achieved only if the initial wild mosquito population is small enough. This is mathematically proved by the local asymptotic stability of the origin, together with the existence of exactly two T-periodic solutions, one of which is asymptotically stable and the other of which is unstable, with T being the waiting period between two consecutive releases. For c is an element of (g(1)*, g(2)*), we find sufficient conditions on the nonexistence of T-periodic solution, and the existence of at most two T-periodic solutions.
Evidence for natural hybridization and novel Wolbachia strain superinfections in the Anopheles gambiae complex from Guinea
16990C. L. Jeffries, C. Cansado-Utrilla, A. H. Beavogui, C. Stica, E. K. Lama, M. Kristan, S. R. Irish and T. Walker, Royal Society Open Science, 8:18. 2021-04-07 14:55:09.
Wolbachia, a widespread bacterium which can influence mosquito-borne pathogen transmission, has recently been detected within Anopheles (An.) species that are malaria vectors in Sub-Saharan Africa. Although studies have reported Wolbachia strains in the An. gambiae complex, apparent low density and prevalence rates require confirmation. In this study, wild Anopheles mosquitoes collected from two regions of Guinea were investigated. In contrast with previous studies, RNA was extracted from adult females (n = 516) to increase the chances for the detection of actively expressed Wolbachia genes, determine Wolbachia prevalence rates and estimate relative strain densities. Molecular confirmation of mosquito species and Wolbachia multilocus sequence typing (MLST) were carried out to analyse phylogenetic relationships of mosquito hosts and newly discovered Wolbachia strains. Strains were detected in An. melas (prevalence rate of 11.6%-16/138) and hybrids between An. melas and An. gambiae sensu stricto (prevalence rate of 40.0%-6/15) from Senguelen in the Maferinyah region. Furthermore, a novel high-density strain, termed wAnsX, was found in an unclassified Anopheles species. The discovery of novel Wolbachia strains (particularly in members, and hybrids, of the An. gambiae complex) provides further candidate strains that could be used for future Wolbachia-based malaria biocontrol strategies.
When More is Less: Mosquito Population Suppression Using Sterile, Incompatible and Genetically Modified Male Mosquitoes
18708S. L. Dobson, Journal of Medical Entomology, 58:1980-1986. 2021-03-11 13:50:08.
The current review of the Sterile Insect Technique (SIT) is motivated by new technologies and the recent renaissance of male release field trials, which is driving an evolution in mosquito control and regulation. Practitioners that are releasing male mosquitoes would do well to learn from past successes and failures, including political and public engagement complications. With examples that include nuanced integrations of the different technologies, e.g., combinations of Wolbachia and irradiation, it is critical that scientists understand and communicate accurately about the technologies, including their evolving management by different regulatory agencies in the USA. Some male release approaches are considered ‘pesticides’ and regulated by federal and state agencies, while other male release approaches are unregulated. It is important to consider how the new technologies fit with the more ‘traditional’ chemical applications of adulticides and larvicides. The economics of male release programs are substantially different from traditional control costs, which can be a challenge to their adoption by abatement districts. However, there is substantial need to overcome these complications and challenges, because the problem with invasive mosquitoes grows ever worse with factors that include insecticide resistance, globalization and climate change.
Number of Project Wolbachia mosquitoes released is constantly reviewed to maintain suppression of dengue: NEA
16388N. L. Ching, today, 2021-02-09 15:12:34.
Project Wolbachia – Singapore has yielded promising results so far.Releases of non-biting male Wolbachia-Aedes mosquitoes have suppressed the urban Aedes aegypti mosquito populations in study sites at Tampines and Yishun by up to 90 per cent, and we have observed 58 to 74 per cent less dengue cases in 2020 in areas where releases have been ongoing for at least a year compared to areas without releases. However, this does not mean that there will be no dengue cases in the study sites, especially in the initial period, because it takes several months for the releases to bring down the dengue mosquito population.While some residents at the release sites have noticed more non-biting mosquitoes around their homes, the released male mosquitoes do not bite, and the overall data shows a clear benefit — fewer dengue cases.
GeneConvene Global Collaborative Webinar Series | Genetic Biocontrol 2021
16249David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2021-02-05 21:53:11.
In the mid 20th century various ideas emerged concerning how genetics and genetic principles could be directly applied to age-old problems of managing insects that threaten food security and public health. This series of webinars will explore the current state-of-the-art of what has been termed genetic control, genetic pest management and genetic biocontrol. It will cover the use of sterility, conditional dominant lethality and Wolbachia-induced cytoplasmic incompatibility. Gene drive, another type of genetic biocontrol, will not be covered in this series; it was recently the focus of webinar series dedicated to the topic.
How to engage communities on a large scale? Lessons from World Mosquito Program in Rio de Janeiro, Brazil [version 2; peer review: 1 approved, 2 approved with reservations]
16361G. B. Costa, R. Smithyman, S. L. O'Neill and L. A. Moreira, Gates Open Research, 2021-02-04 19:26:09.
Here we discuss and analyse the framework for community engagement implemented by the WMP in Brazil, during the large-scale deployment of the method in the municipalities of Niterói and Rio de Janeiro, Brazil. Our experience indicates that the community engagement work for arboviruses control should be understood as an opportunity for local development. It is necessary, based on an integrated analysis of the territory, to understand that the actions for arboviruses control could be a catalyst for the necessary socioenvironmental, cultural and public health changes. Furthermore, it is essential to understand that community engagement goes beyond informing or asking for population consent, but it constitutes a possibility for dialogue and exchange between the various stakeholders present in the territories, to build on cooperation for mosquito-borne disease control.
Reply to: Issues with combining incompatible and sterile insect techniques
16265Y. Li, L. A. Baton, D. Zhang, J. Bouyer, A. G. Parker, A. A. Hoffmann, L. C. Ng, C. H. Tan and Z. Xi, Nature, 590:E3-E5. 2021-02-04 16:31:29.
When the aim is elimination of the target population, Uni-CI and Bi-CI do not have appreciably different risks of population replacement. The small-scale field trial8 cited by Moretti and Calvitti in their Comment1 does not provide evidence that Bi-CI protects against population replacement during IIT, as the occurrence of the released Wolbachia strain in the field was not determined and the level of population suppression was insufficient to facilitate surpassing of the invasion threshold.
Issues with combining incompatible and sterile insect techniques
16261R. Moretti and M. Calvitti, Nature, 590:E1-E2. 2021-02-03 16:00:45.
In a recent paper, Zheng at al.1 performed field experiments that tested a strategy of mosquito suppression based on the release of functionally sterile males produced by the combination of reproductive unidirectional cytoplasmic incompatibility (which is induced by the bacterium Wolbachia) and a sterilization treatment caused by X-rays. In our opinion, the authors do not present an exhaustive description of the current status in this field, and their results highlight several practical weaknesses in this strategy.
Project Wolbachia: Residents are killing the ‘helpful’ mosquitoes, which can be a nuisance
16228T. J. Cheng, today, 2021-01-29 16:33:12.
In 2019, Dr Amy Khor, then Senior Minister of State for the Environment and Water Resources, said that there was a 90 per cent suppression rate at study sites in Tampines and Yishun from February to November that year. However, certain public housing estates under the project were still dengue hot zones last year.The idea of the project is to have the male Aedes mosquitoes, which are injected with the Wolbachia bacteria, mate with female Aedes aegypti mosquitoes. The females then go on to lay eggs that do not hatch, effectively suppressing their numbers.
Demographic feedbacks can hamper the spatial spread of a gene drive
16203L. Girardin and F. Débarre, arXiv, 2021-01-27 15:32:53.
Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
Next-generation tools to control biting midge populations and reduce pathogen transmission
15940P. Shults, L. W. Cohnstaedt, Z. N. Adelman and C. Brelsfoard, Parasites and Vectors, 14:31. 2021-01-07 14:52:23.
Biting midges of the genus Culicoides transmit disease-causing agents resulting in a significant economic impact on livestock industries in many parts of the world. Localized control efforts, such as removal of larval habitat or pesticide application, can be logistically difficult, expensive and ineffective if not instituted and maintained properly. With these limitations, a population-level approach to the management of Culicoides midges should be investigated as a means to replace or supplement existing control strategies. Next-generation control methods such as Wolbachia- and genetic-based population suppression and replacement are being investigated in several vector species. Here we assess the feasibility and applicability of these approaches for use against biting midges. We also discuss the technical and logistical hurdles needing to be addressed for each method to be successful, as well as emphasize the importance of addressing community engagement and involving stakeholders in the investigation and development of these approaches.
Genetic pest management and the background genetics of release strains
15695P. T. Leftwich, L. G. Spurgin, T. Harvey-Samuel, C. J. E. Thomas, L. C. Paladino, M. P. Edgington and L. Alphey, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190805. 2020-12-28 15:35:20.
We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti
15689N. A. Ahmad, M.-V. Mancini, T. H. Ant, J. Martinez, G. M. R. Kamarul, W. A. Nazni, A. A. Hoffmann and S. P. Sinkins, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190809. 2020-12-28 15:06:28.
Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands.
Modelling the Wolbachia incompatible insect technique: strategies for effective mosquito population elimination
15281D. E. Pagendam, B. J. Trewin, N. Snoad, S. A. Ritchie, A. A. Hoffmann, K. M. Staunton, C. Paton and N. Beebe, BMC Biology, 18:13. 2020-12-02 16:29:23.
We introduce a simple Markov population process model for studying mosquito populations subjected to a Wolbachia-IIT programme which exhibit an unstable equilibrium threshold. The model is used to study, in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasing Wolbachia-infected females while reducing costs.
Reply to: “Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported”
15264C. Souto-Maior, J. G. King, L. M. Sartori, R. Maciel-de-Freitas and M. G. M. Gomes, Nature Communications, 11:6113. 2020-11-30 19:09:46.
Ant et al.4 claim that concerns with the data and broader analysis make our conclusions misleading. We herein respond to their comments by demonstrating the robustness of our results to different treatments of the data, and expand our arguments for replacing currently adopted methods by those introduced in our paper.
Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported
15258T. H. Ant, M.-V. Mancini, J. Martinez and S. P. Sinkins, Nature Communications, 11:6111. 2020-11-30 18:48:33.
King et al.3 used DENV infection and transmission modelling to reinterpret experimental data from two previous studies4,5. The authors claimed that wMel Wolbachia increase the mean susceptibility of Ae. aegypti to DENV, contradicting various other studies6,7,8,9,10,11,12. Here, we raise concerns with the experimental approaches used to generate one of the primary datasets on which the modelling is based, and we discuss how these limitations could make some of the original conclusions misleading.
Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies
15960E. M. Rocha, R. D. Katak, J. C. de Oliveira, M. D. Araujo, B. C. Carlos, R. Galizi, F. Tripet, O. Marinotti and J. A. Souza, Tropical Medicine and Infectious Disease, 5. 2020-10-20 18:16:39.
Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.
Selfish genetic elements and male fertility
15183R. L. Verspoor, T. A. R. Price and N. Wedell, Philosophical Transactions of the Royal Society B-Biological Sciences, 375:7. 2020-10-20 14:40:03.
Selfish genetic elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here, we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex ratios and in particular reducing sperm-competitive success of SGE-carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely. This article is part of the theme issue 'Fifty years of sperm competition'.
Stable Introduction of Plant-Virus-Inhibiting Wolbachia into Planthoppers for Rice Protection
19719J. T. Gong, Y. Li, T. P. Li, Y. Liang, L. Hu, D. Zhang, C. Y. Zhou, C. Yang, X. Zhang, S. S. Zha, X. Z. Duan, L. A. Baton, X. Y. Hong, A. A. Hoffmann and Z. Xi, Current Biology, 30:4837-4845.e5. 2020-10-10 12:20:07.
Progress has been made in developing the maternally inherited endosymbiotic bacterium Wolbachia as a tool for protecting humans from mosquito-borne diseases. In contrast, Wolbachia-based approaches have not yet been developed for the protection of plants from insect pests and their associated diseases, with a major challenge being the establishment of artificial Wolbachia infections expressing desired characteristics in the hemipterans that transmit the majority of plant viruses. Here, we report stable introduction of Wolbachia into the brown planthopper, Nilaparvata lugens, the most destructive rice pest that annually destroys millions of hectares of staple crops. The Wolbachia strain wStri from the small brown planthopper, Laodelphax striatellus, was transferred to this new host, where it showed high levels of cytoplasmic incompatibility, enabling rapid invasion of laboratory populations. Furthermore, wStri inhibited infection and transmission of Rice ragged stunt virus and mitigated virus-induced symptoms in rice plants, opening up the development of Wolbachia-based strategies against major agricultural pests and their transmitted pathogens
Microbiome Innovation in Agriculture: Development of Microbial Based Tools for Insect Pest Management
19716M. Qadri, S. Short, K. Gast, J. Hernandez and A. C.-N. Wong, Frontiers in Sustainable Food Systems, 4. 2020-10-06 12:11:19.
This review emphasizes the potential and use of microbes in sustainable insect pest management. We first review the diverse insect traits shaped by insect-microbe associations that span nutrition, immunity, ecological interactions with natural enemy, insecticide resistance, and behavior. This is followed by discussing different microbiome manipulation approaches to alter pest traits, describing some of the opportunities and obstacles for each approach. We then highlight microbiomes as untapped chemical inventories to discover novel biopesticides, including plant-incorporated protectants and semiochemicals. The last topic covered is the use of beneficial microbes to improve mass-reared insects' performance for autocidal programs, including sterile insect technique and incompatible insect technique, in which we identify topics where data are limited or inconclusive, for future research.
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
The Evolving Arsenal Against Mosquito-Born Diseases
14369J. Smith, Labiotech.eu, 2020-09-10 16:01:02.
As the global climate continues to warm, disease-spreading mosquitoes such as Aedes aegypti are expected to establish themselves in the US and Europe.
Prospects and Pitfalls: Next-Generation Tools to Control Mosquito-Transmitted Disease
14366E. P. Caragata, S. Dong, Y. Dong, M. L. Simões, C. V. Tikhe and G. Dimopoulos, Annual Review of Microbiology, 74:455-475. 2020-09-08 15:57:19.
A diverse array of next-generation tools has been designed to eliminate mosquito populations or to replace them with mosquitoes that are less capable of transmitting key pathogens.
How to fight the deadly dengue virus? Make your own mosquitoes
14320J. Emont, Wall Street Journal, 2020-09-07 15:13:25.
When the bacteria-laden male mosquitoes are released into the open and mate with naturally-born females, the resultant eggs won’t hatch.
Non-GMO approach reduces cases of mosquito-borne dengue by 77%
14239GM Watch, GM Watch, 2020-08-31 13:55:39.
A randomized field trial found that mosquitoes infected with a natural bacterium called Wolbachia reduced cases of dengue by an "extraordinary" 77%.
Bacteria-Laced Mosquitoes Limit Spread of Dengue
14244A. Heidt, The Scientist, 2020-08-29 14:05:32.
Researchers have infected Aedes aegypti mosquitoes—the species responsible for passing on many diseases—with bacteria called Wolbachia with the intent of reducing the insects’ ability to pass on dengue to people.
Scientists infect mosquitoes with bacteria to stop the transmission of dengue fever in Indonesia, dropping infection rates by 77 percent
14250D. Avery, Daily Mail, 2020-08-28 14:15:52.
The team found that dengue infections were 77 percent lower in treated neighborhoods, compared to areas not exposed to the infected insects.
The mosquito strategy that could eliminate dengue
14170E. Callaway, Nature, 2020-08-27 14:19:52.
The study, conducted in an Indonesia city, showed that releasing mosquitoes modified to carry a bacterium called Wolbachia, which stops the insects from transmitting some viruses, led to a steep drop in cases of dengue fever.
Researchers Find New Approach To Control Dengue, Zika By Genetically Modifying Mosquitoes
14247N. Sharma, R. Republicworld.com, 2020-08-27 14:11:56.
A new study carried out in Indonesia has shown that dengue infection rates decreased in regions where the genetically modified mosquitoes were introduced.
Australian research takes aim at dengue, another killer virus
14226E. Connors, Finanacial Review, 2020-08-26 20:22:39.
Australian researchers have teamed up with Indonesian philanthropists to strike a blow against dengue fever, the deadly disease that was a growing scourge in south-east Asia and South America long before COVID-19.
Australian scientists slash dengue fever in Indonesia by infecting mosquitoes with bacteria
14224A. Barker, ABC News, 2020-08-26 20:17:56.
Australian scientists may have found the secret to eradicating dengue fever, with a lengthy trial in Indonesia drastically reducing the incidence of the mosquito-borne virus.
Fighting mosquito-borne diseases… with mosquitoes
14156N. Gubert and A. Baubeau, Phys Org, 2020-08-26 13:13:41.
For decades, researchers have scratched their heads over how to combat deadly mosquito-borne diseases such as dengue fever.
Cytoplasmic incompatibility: an autocidal mechanism for mosquito population control
13893V. Dev, BugBitten BMC, 2020-08-18 13:23:13.
Cytoplasmic incompatibility resulting in non-reciprocal fertility is a naturally occurring phenomenon, but remains unexplored to greater extent for the control of insect vector populations. This mechanism deserves priority for mosquito control and reducing disease transmission, being non-insecticidal and easier to operate with minimal investments.
Modeling the suppression dynamics of Aedes mosquitoes with mating inhomogeneity
13847M. Huang and L. Hu, Journal of Biological Dynamics, 14:656-678. 2020-08-04 13:51:41.
In this work, we introduce a delay differential equation model with mating inhomogeneity to discuss mosquito population suppression based on Wolbachia. Our analyses show that the wild mosquitoes could be eliminated if either the adult mortality rate exceeds the threshold δ∗A or the release amount exceeds the threshold r∗ uniformly. Our simulations suggest that the releasing should be started at least 5 weeks before the peak dengue season, taking into account both the release amount and the suppression speed.
The Biochemistry of Cytoplasmic Incompatibility Caused by Endosymbiotic Bacteria
18757H. Chen, M. Zhang and M. Hochstrasser, Genes, 11. 2020-07-25 14:17:05.
Many species of arthropods carry maternally inherited bacterial endosymbionts that can influence host sexual reproduction to benefit the bacterium. The most well-known of such reproductive parasites is Wolbachia pipientis. Wolbachia are obligate intracellular α-proteobacteria found in nearly half of all arthropod species. This success has been attributed in part to their ability to manipulate host reproduction to favor infected females. Cytoplasmic incompatibility (CI), a phenomenon wherein Wolbachia infection renders males sterile when they mate with uninfected females, but not infected females (the rescue mating), appears to be the most common. CI provides a reproductive advantage to infected females in the presence of a threshold level of infected males. The molecular mechanisms of CI and other reproductive manipulations, such as male killing, parthenogenesis, and feminization, have remained mysterious for many decades. It had been proposed by Werren more than two decades ago that CI is caused by a Wolbachia-mediated sperm modification and that rescue is achieved by a Wolbachia-encoded rescue factor in the infected egg. In the past few years, new research has highlighted a set of syntenic Wolbachia gene pairs encoding CI-inducing factors (Cifs) as the key players for the induction of CI and its rescue. Within each Cif pair, the protein encoded by the upstream gene is denoted A and the downstream gene B. To date, two types of Cifs have been characterized based on the enzymatic activity identified in the B protein of each protein pair; one type encodes a deubiquitylase (thus named CI-inducing deubiquitylase or cid), and a second type encodes a nuclease (named CI-inducing nuclease or cin). The CidA and CinA proteins bind tightly and specifically to their respective CidB and CinB partners. In transgenic Drosophila melanogaster, the expression of either the Cid or Cin protein pair in the male germline induces CI and the expression of the cognate A protein in females is sufficient for rescue. With the identity of the Wolbachia CI induction and rescue factors now known, research in the field has turned to directed studies on the molecular mechanisms of CI, which we review here.
Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes
13600S. A. Ford, I. Albert, S. L. Allen, S. F. Chenoweth, M. Jones, C. Koh, A. Sebastian, L. T. Sigle and E. A. McGraw, Frontiers in Microbiology, 11:1456. 2020-07-07 13:18:12.
We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking.
Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes
13607P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller, Journal of Applied Ecology, 11. 2020-06-18 12:44:16.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this transgene in large cages using a joint experimental modelling approach. We performed a 4-month experiment in large, indoor cages to study the population genetics of the transgene.
Genetic Biocontrol – An Overview (video 13.13 min)
11398GeneConvene Global Collaborative, 2020-04-25 12:41:00.
This video explains what genetic biocontrol is and surveys various technologies that can be consider genetic biocontrol technologies. It offers a conceptual organization of the various technologies based on the potential of genetic biocontrol organisms to persist and spread in an environment. This video was produced by the GeneConvene Global Colaborative.
Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically
12383H. Dahmana and O. Mediannikov, Pathogens, 9:26. 2020-04-23 17:49:22.
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance.
Can we kill the dreaded mosquito? Do we even want to?
11228Stacey McKenna, Sierra, 2020-04-19 15:40:08.
As a major vector for disease, the mosquito has harmed more human beings than just about any other animal, and a changing climate is only boosting those numbers. As the range of disease-carrying species of mosquitoes expands, so does their ability to transmit the parasites and viruses that result in malaria, chikungunya, Zika, yellow fever, West Nile, and dengue fever. In 2018, the continental United States saw a 25 percent increase in severe, neuroinvasive cases of West Nile virus compared with a decade earlier. And over the past three decades, the CDC reports, the worldwide incidence of dengue fever has risen 30-fold.
Selfish genes and sexual selection: the impact of genomic parasites on host reproduction
11970N. Wedell, Journal of Zoology, 311:1-12. 2020-04-08 18:18:42.
Selfish genetic elements (SGEs) such as replicating mobile elements, segregation distorters and maternally inherited endosymbionts, bias their transmission success relative to the rest of the genome to increase in representation in subsequent generations. As such, they generate conflict with the rest of the genome. Such intragenomic conflict is also a hallmark of sexually antagonistic (SA) alleles, which are shared genes between the sexes but that have opposing fitness effects when expressed in males and females. However, whilst both SGEs and SA alleles are recognized as common and potent sources of genomic conflict, the realization that SGEs can also generate sexually antagonistic selection and contribute to sexual conflict in addition to generate sexual selection is largely overlooked. Here, I show that SGEs frequently generate sex-specific selection and outline how SGEs that are associated with compromised male fertility can shape female mating patterns, play a key role in the dynamics of sex-determination systems and likely be an important source of sexually antagonistic genetic variation. Given the prevalence of SGEs, their contribution to sexual conflict is likely to be greatly overlooked.
Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations
22639J. E. Crawford, D. W. Clarke, V. Criswell, M. Desnoyer, D. Cornel, B. Deegan, K. Gong, K. C. Hopkins, P. Howell, et al., Nature Biotechnology, 38:482-492. 2020-04-06 06:19:43.
The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6–96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs.
The potential cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: a modelling study
14326O. J. Brady, D. D. Kharisma, N. N. Wilastonegoro, K. M. Reilly, E. Hendricx, L. S. Bastos, L. Yakob and D. S. Shepard, medRxiv, 2020.01.11.20017186. 2020-01-16 17:55:32.
Wolbachia releases in high density urban areas is expected to be highly cost-effective and could potentially be the first cost saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritized.
Wolbachia transinfections in Culex quinquefasciatus generate cytoplasmic incompatibility
6224T. H. Ant, C. Herd, F. Louis, A. B. Failloux and S. P. Sinkins, Insect Molecular Biology, 29:1-8. 2020-01-06 21:43:12.
Culex quinquefasciatus is an important mosquito vector of a number of viral and protozoan pathogens of humans and animals, and naturally carries the endosymbiont Wolbachia pipientis, strain wPip. Wolbachia are used in two distinct vector control strategies: firstly, population suppression caused by mating incompatibilities between mass-released transinfected males and wild females; and secondly, the spread of pathogen transmission-blocking strains through populations. Using embryonic microinjection, two novel Wolbachia transinfections were generated in C. quinquefasciatus using strains native to the mosquito Aedes albopictus: a wAlbB single infection, and a wPip plus wAlbA superinfection. The wAlbB infection showed full bidirectional cytoplasmic incompatibility (CI) with wild-type C. quinquefasciatus in reciprocal crosses. The wPipwAlbA superinfection showed complete unidirectional CI, and therefore population invasion potential. Whereas the wAlbB strain showed comparatively low overall densities, similar to the native wPip, the wPipwAlbA superinfection reached over 400-fold higher densities in the salivary glands compared to the native wPip, suggesting it may be a candidate for pathogen transmission blocking.
Malaysia Wolbachia trials: Battling dengue and other mosquito-borne viruses
170592019-11-22 13:47:09.
Establishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control
17089W. A. Nazni, A. A. Hoffmann, A. NoorAfizah, Y. L. Cheong, M. V. Mancini, N. Golding, G. M. R. Kamarul, M. A. K. Arif, H. Thohir, H. NurSyamimi, M. Z. ZatilAqmar, M. NurRuqqayah, A. NorSyazwani, A. Faiz, F.-R. M. N. Irfan, S. Rubaaini, N. Nuradila, N. M. N, Current Biology, 29:4241-4248.e5. 2019-11-21 15:20:44.
Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates.
Incompatible and sterile insect techniques combined eliminate mosquitoes
16263X. Zheng, D. Zhang, Y. Li, C. Yang, Y. Wu, X. Liang, Y. Liang, X. Pan, L. Hu, Q. Sun, X. Wang, Y. Wei, J. Zhu, W. Qian, Z. Yan, A. G. Parker, J. R. L. Gilles, K. Bourtzis, J. Bouyer, M. Tang, B. Zheng, J. Yu, J. Liu, J. Zhuang, Z. Hu, M. Zhang, J.-T. Gon, 572, 56-61. 2019-07-17 16:15:33.
Here we show that combining incompatible and sterile insect techniques (IIT–SIT) enables near elimination of field populations of the world’s most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT–SIT for mosquito vector control.
Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs
3895Buchman, AG, S.; Li, M.; Antoshechkin, I.; Li, H. H.; Wang, H. W.; Chen, C. H.; Klein, M. J.; Duchemin, J. B.; Paradkar, P. N.; Akbari, O. S., Proceedings of the National Academy of Sciences of the United States of America, 116:3656-3661. 2019-01-13 00:00:00.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.
The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications
3889Beckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019-01-07 00:00:00.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin–antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in Drosophila
3944Shropshire, JDB, S. R., PLOS Genetics, 15:e1008221. 2019-01-02 00:00:00.
Wolbachia are maternally inherited bacteria that infect arthropod species worldwide and are deployed in vector control to curb arboviral spread using cytoplasmic incompatibility (CI). CI kills embryos when an infected male mates with an uninfected female, but the lethality is rescued if the female and her embryos are likewise infected. Two phage WO genes, cifA(wMel) and cifB(wMel) from the wMel Wolbachia deployed in vector control, transgenically recapitulate variably penetrant CI, and one of the same genes, cifA(wMel), rescues wild type CI. The proposed Two-by-One genetic model predicts that CI and rescue can be recapitulated by transgenic expression alone and that dual cifA(wMel) and cifB(wMel) expression can recapitulate strong CI. Here, we use hatch rate and gene expression analyses in transgenic Drosophila melanogaster to demonstrate that CI and rescue can be synthetically recapitulated in full, and strong, transgenic CI comparable to wild type CI is achievable. These data explicitly validate the Two-by-One model in wMel-infected D. melanogaster, establish a robust system for transgenic studies of CI in a model system, and represent the first case of completely engineering male and female animal reproduction to depend upon bacteriophage gene products. Author summary Releases of Wolbachia-infected mosquitos are underway worldwide because Wolbachia block replication of Zika and Dengue viruses and spread themselves maternally through arthropod populations via cytoplasmic incompatibility (CI). The CI drive system depends on a Wolbachia-induced sperm modification that results in embryonic lethality when an infected male mates with an uninfected female, but this lethality is rescued when the female and her embryos are likewise infected. We recently reported that the phage WO genes, cifA and cifB, cause the sperm modification and cifA rescues the embryonic lethality caused by the wMel Wolbachia strain deployed in vector control. These reports motivated proposal of the Two-by-One model of CI whereby two genes cause lethality and one gene rescues it. Here we provide unequivocal support for the model in the Wolbachia strain used in vector control via synthetic methods that recapitulate CI and rescue in the absence of a Wolbachia infections. Our results reveal the set of phage WO genes responsible for this powerful genetic drive system, act as a proof-of-concept that these genes alone can induce gene drive like crossing patterns, and establish methodologies and hypotheses for future studies of CI in Drosophila. We discuss the implications of the Two-by-One model towards functional mechanisms of CI, the emergence of incompatibility between Wolbachia strains, vector control applications, and CI gene nomenclature.
One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster
5926Shropshire, J. D., J. On, E. M. Layton, H. Zhou and S. R. Bordenstein, Proceedings of the National Academy of Sciences, 115:4987. 2018-04-23 16:58:30.
The World Health Organization recommended pilot deployment of Wolbachia-infected mosquitoes to curb viral transmission to humans. Releases of mosquitoes are underway worldwide because Wolbachia can block replication of these pathogenic viruses and deterministically spread by a drive system termed cytoplasmic incompatibility (CI). Despite extensive research, the underlying genetic basis of CI remains only half-solved. We recently reported that two prophage WO genes recapitulate the modification component of CI in a released strain for vector control. Here we show that one of these genes underpins rescue of CI. Together, our results reveal the complete genetic basis of this selfish trait and pave the way for future studies exploring WO prophage genes as adjuncts or alternatives to current control efforts.Wolbachia are maternally inherited, intracellular bacteria at the forefront of vector control efforts to curb arbovirus transmission. In international field trials, the cytoplasmic incompatibility (CI) drive system of wMel Wolbachia is deployed to replace target vector populations, whereby a Wolbachia-induced modification of the sperm genome kills embryos. However, Wolbachia in the embryo rescue the sperm genome impairment, and therefore CI results in a strong fitness advantage for infected females that transmit the bacteria to offspring. The two genes responsible for the wMel-induced sperm modification of CI, cifA and cifB, were recently identified in the eukaryotic association module of prophage WO, but the genetic basis of rescue is unresolved. Here we use transgenic and cytological approaches to demonstrate that maternal cifA expression independently rescues CI and nullifies embryonic death caused by wMel Wolbachia in Drosophila melanogaster. Discovery of cifA as the rescue gene and previously one of two CI induction genes establishes a “Two-by-One” model that underpins the genetic basis of CI. Results highlight the central role of prophage WO in shaping Wolbachia phenotypes that are significant to arthropod evolution and vector control.
Evolutionary genetics of cytoplasmic incompatibility genes cifA and cifB in prophage WO of Wolbachia
5929Lindsey, A. R. I., D. W. Rice, S. R. Bordenstein, A. W. Brooks, S. R. Bordenstein and I. L. G. Newton, Genome Biology and Evolution, 10:434-451. 2018-01-17 17:04:14.
The bacterial endosymbiont Wolbachia manipulates arthropod reproduction to facilitate its maternal spread through host populations. The most common manipulation is cytoplasmic incompatibility (CI): Wolbachia-infected males produce modified sperm that cause embryonic mortality, unless rescued by embryos harboring the same Wolbachia. The genes underlying CI, cifA and cifB, were recently identified in the eukaryotic association module of Wolbachia’s prophage WO. Here, we use transcriptomic and genomic approaches to address three important evolutionary facets of the cif genes. First, we assess whether or not cifA and cifB comprise a classic toxin–antitoxin operon in wMel and show that the two genes exhibit striking, transcriptional differences across host development. They can produce a bicistronic message despite a predicted hairpin termination element in their intergenic region. Second, cifA and cifB strongly coevolve across the diversity of phage WO. Third, we provide new domain and functional predictions across homologs within Wolbachia, and show that amino acid sequences vary substantially across the genus. Finally, we investigate conservation of cifA and cifB and find frequent degradation and loss of the genes in strains that no longer induce CI. Taken together, we demonstrate that cifA and cifB exhibit complex transcriptional regulation in wMel, provide functional annotations that broaden the potential mechanisms of CI induction, and report recurrent erosion of cifA and cifB in non-CI strains, thus expanding our understanding of the most widespread form of reproductive parasitism.
Rapid comeback of males: evolution of male-killer suppression in a green lacewing population
3979Hayashi, MN, M.; Kageyama, D., Proceedings of the Royal Society B-Biological Sciences, 285:6. 2018-01-17 00:00:00.
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi. An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
Genetics and genomics of an unusual selfish sex ratio distortion in an insect
3976Hamilton, PTH, C. N.; Curtis, C. I.; Perlman, S. J., Current Biology, 28:3864-3870. 2018-01-14 00:00:00.
Diverse selfish genetic elements have evolved the ability to manipulate reproduction to increase their transmission, and this can result in highly distorted sex ratios [1]. Indeed, one of the major explanations for why sex determination systems are so dynamic is because they are shaped by ongoing coevolutionary arms races between sex-ratio-distorting elements and the rest of the genome [2]. Here, we use genetic crosses and genome analysis to describe an unusual sex ratio distortion with striking consequences on genome organization in a booklouse species, Liposcelis sp. (Insecta: Psocodea), in which two types of females coexist. Distorter females never produce sons but must mate with males (the sons of nondistorting females) to reproduce [3]. Although they are diploid and express the genes inherited from their fathers in somatic tissues, distorter females only ever transmit genes inherited from their mothers. As a result, distorter females have unusual chimeric genomes, with distorter-restricted chromosomes diverging from their nondistorting counterparts and exhibiting features of a giant non-recombining sex chromosome. The distorter-restricted genome has also acquired a gene from the bacterium Wolbachia, a well-known insect reproductive manipulator; we found that this gene has independently colonized the genomes of two other insect species with unusual reproductive systems, suggesting possible roles in sex ratio distortion in this remarkable genetic system.
SCIENTIFIC OPINION: In response to the referral of 12 October 2015 concerning use of genetically modified mosquitoes for vector control
16065High Council for Biotechnology, High Council for Biotechnology (France), 2017-05-31 13:46:03.
The Scientific Committee’s opinion describes emerging vector control techniques using GM mosquitoes, the current state of research into and development of these techniques and the outcomes of initial experiments worldwide. To date, only one technique has been developed to an operational level: Oxitec’s RIDL technique, which sets out to reduce a mosquito population by repeated mass releases of sterilising transgenic males. Two other techniques at an earlier stage of research and development are based on gene drive, seeking to spread a genetic trait in a wild population, either to make the mosquitoes incapable of transmitting pathogens (gene drive for population modification) or to eliminate the population by spreading sterility (gene drive for population elimination).
A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility
5932Beckmann, J. F., J. A. Ronau and M. Hochstrasser, Nature Microbiology, 2:17007. 2017-03-01 17:45:04.
Wolbachia are obligate intracellular bacteria1 that infect arthropods, including approximately two-thirds of insect species2. Wolbachia manipulate insect reproduction by enhancing their inheritance through the female germline. The most common alteration is cytoplasmic incompatibility (CI)3–5, where eggs from uninfected females fail to develop when fertilized by sperm from Wolbachia-infected males. By contrast, if female and male partners are both infected, embryos are viable. CI is a gene-drive mechanism impacting population structure6 and causing reproductive isolation7, but its molecular mechanism has remained unknown. We show that a Wolbachia deubiquitylating enzyme (DUB) induces CI. The CI-inducing DUB, CidB, cleaves ubiquitin from substrates and is encoded in a two-gene operon, and the other protein, CidA, binds CidB. Binding is strongest between cognate partners in cidA-cidB homologues. In transgenic Drosophila, the cidA-cidB operon mimics CI when sperm introduce it into eggs, and a catalytically inactive DUB does not induce sterility. Toxicity is recapitulated in yeast by CidB alone; this requires DUB activity but is rescued by coexpressed CidA. A paralogous operon involves a putative nuclease (CinB) rather than a DUB. Analogous binding, toxicity and rescue in yeast were observed. These results identify a CI mechanism involving interacting proteins that are secreted into germline cells by Wolbachia, and suggest new methods for insect control.
Genetic conflicts: the usual suspects and beyond
4058McLaughlin, RNM, H. S., Journal of Experimental Biology, 220:6-17. 2017-01-16 00:00:00.
Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements.
Advances in vector control science: Rear-and-release strategies show promise… but don’t forget the basics
4065Ritchie, SAJ, B. J., Journal of Infectious Diseases, 215:S103-S108. 2017-01-03 00:00:00.
Both chikungunya and Zika viruses have recently swept from Africa across the Pacific to the Americas, causing major outbreaks of disease in humans. In the meantime, dengue epidemics continue throughout the tropics. Traditional vector control programs based on strategies from 1950s and 1960s have been relatively ineffective in combating recent epidemics. In response, new methods involving the rearing and releasing of large numbers of mosquitoes to eliminate or modify local Aedes populations are being developed, with several currently conducting field releases in high-risk countries. These advances, include the release of Wolbachia-infected Aedes aegypti and Aedes albopictus, for either its virus-blocking capabilities, sterilization by cytoplasmic incompatibility, or both; the release of Aedes carrying dominant lethal genes, such as the OX513A strain of A. aegypti; and other emerging techniques, such as advancing gene-drive technologies, are summarized, as well as current stages of development and primary operational and regulatory hurdles. Although these technologies show great promise, none are ready for widespread rollout for cities of millions of people. Thus, efforts should be made to avoid methods such as space sprays that have failed and improve existing technologies to increase their efficacy.
TSETSE GENETICS: Contributions to Biology, Systematics, and Control of Tsetse Flies
26199R. H. Gooding and E. S. Krafsur, Annual Review of Entomology, 50:101-123. 2005-01-01 14:04:26.
Tsetse flies (Diptera: Glossinidae) constitute a small, ancient taxon of exclusively hematophagous insects that reproduce slowly and viviparously. Because tsetse flies are the only vectors of pathogenic African trypanosomes, they are a potent and constant threat to humans and livestock over much of sub-Saharan Africa. Despite their low fecundity, tsetse flies demonstrate great resilience, which makes population suppression expensive, transient, and beyond the capacities of private and public sectors to accomplish, except over small areas. Nevertheless, control measures that include genetic methods are under consideration at national and supranational levels. There is a pressing need for sufficient laboratory cultures of tsetse flies and financial support to carry out genetic research. Here we review tsetse genetics from organismal and population points of view and identify some research needs.
To what extent do different types of sex ratio distorters interfere?
4288Engelstadter, JM, H.; Hurst, G. D. D., Evolution, 58:2382-2386. 2004-01-06 00:00:00.
Within the Diptera, two different selfish genetic elements are known to cause the production of female-biased sex ratios: maternally inherited bacteria that kill male zygotes (male-killers), and X chromosomes causing the degeneration of Y-bearing sperm in males (meiotic drive). We here develop a mathematical model for the dynamics of these two sex-ratio distorters where they co-occur. We show that X chromosome meiotic drive elements can be expected to substantially lower the equilibrium frequency of male-killers and can even lead to their extinction. Conversely, male-killers can also decrease the equilibrium frequency of X drivers and cause their extinction. Thus, we predict that there will be some complementarity in the incidence of X chromosome meiotic drive and male-killing in natural populations, with a lower than expected number of species bearing both elements.
Persistence of an extreme sex-ratio bias in a natural population
4287Dyson, EAH, G. D. D., Proceedings of the National Academy of Sciences of the United States of America, 101:6520-6523. 2004-01-05 00:00:00.
The sex ratio is a key parameter in the evolution and ecology of a species. Selfish genetic elements that bias the sex ratio of affected individuals are well known and characterized, but their effect on populations has been considered limited, because either the element does not achieve high prevalence or the host rapidly evolves resistance to the distorting element, reducing its prevalence. We tested whether the host necessarily prevails by using a butterfly system where records from the early part of the 20th century reported extreme sex-ratio bias in nature. We reexamined this population and found the bias was present today, 400 generations after the original record, with a population sex ratio of 100 females per male. The sex-ratio bias was associated with the presence of a heritable male-killing Wolbachia infection in 99% of adult females, against which the host butterfly has failed to evolve resistance. The resultant dearth of males causes an average 57% reduction in the reproductive output of adult females. Persistence of the population despite the very high frequency of the sex-ratio distorter appears to be associated with the ability of males to mate >50 times in their life combined with a high intrinsic rate of increase of the species.
Wolbachia as a possible means of driving genes into populations
4368Curtis, CFS, S. P., Parasitology, 116:S111-S115. 1998-01-06 00:00:00.
Cytoplasmic incompatibility consists of sterility in cross matings, the crossing type being maternally inherited. It can be explained by the action of Wolbachia symbionts which are transmitted through the egg cytoplasm and leave an imprint on the sperm which prevents it fertilizing unless it is 'rescued' by the action of the same type of Wolbachia in the egg. Thus matings between infected males and uninfected females are sterile, but the reciprocal matings are fertile. Hence uninfected females are at risk of failing to transmit their uninfected cytoplasm if they cross mate, but infected females are at no such risk. Therefore natural selection favours the infected state and in two wild insect populations the infection has been observed spreading. If a gene for inability to transmit malaria could be introduced into Wolbachia and if this could be introduced into Anopheles (where these symbionts appear not to occur naturally), release of a limited number of such insects should trigger a process of displacement of malaria vectors, by the non-vector type. A simple model is used to demonstrate the limitations to this process which would be introduced by immigration.
Population replacement in Culex-fatigans by means of cytoplasmic incompatibility .2. Field cage experiments with overlapping generations
6276C. F. Curtis, Bulletin of the World Health Organization, 53:107-119. 1976-01-08 16:51:11.
Three experiments were carried out in field cages to test the principle of " transport" of a desirable gene or chromosome into a wild Culex fatigans population as a result of the sterility in cross-matings associated with cytoplasmic incompatibility. Cycling populations of Delhi origin were established in the cages and daily releases were made of the IS31B strain, which has Paris cytoplasm and carries a male-linked translocation. It was shown that, if sufficient releases were made to establish a majority of the Paris cytoplasmic type, complete replacement by this cytoplasmic type subsequently occurred. However, as a result of partial compatibility of males of the Delhi population with Paris females, " recombinant " males with Paris cytoplasm and no translocation were produced. In an experiment in which a continuous low rate of " immigration " of a strain of Delhi origin was simulated, a gradual increase of the Paris cytoplasm non-translocated type occurred, and renewed IS31B releases were necessary after 5 months to restore the predominance of this type. The results are compared with computer predictions and discussed in relation to the transport of genes for filaria refractoriness or chromosome translocations into wild populations.
Eradication of Culex pipiens fatigans through cytoplasmic incompatibility.
6278H. Laven, Nature, 216:383. 1967-10-28 16:57:49.
Culex pipiens fatigans is the chief vector of filariasis in south-east Asia. Urbanization has often caused the numbers of this mosquito-and with it the danger of filariasis infection-to increase alarmingly. The natural vigour, tolerance and fast development of resistance to insecticides of this mosquito necessitate the development of other control methods, and cytoplasmic incompatibility2 seems to be an ideal means.
Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org