Keywords: Population modification/replacement
Compound effector genes suppress malaria parasite infections in gene-drive population modification strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
35494Rebeca Carballar-Lejarazú, Yuemei Dong, Thai Binh Pham, et al., G3 Genes|Genomes|Genetics, 2026-03-09 10:43:52.
Malaria remains a major global health burden and is caused by protozoan parasites in the genus Plasmodium. Parasites are transmitted to humans during blood feeding by anopheline mosquitoes, and members of the Anopheles gambiae species complex are important vectors in sub-Saharan Africa. Gene-drive technologies offer promising options for disease control by enabling the spread of genetic traits through mosquito populations that block parasite transmission. We report here the development and characterization of four population modification gene-drive strains in Anopheles gambiae s.s. and An. coluzzii carrying compound effector genes. We sought to enhance the effectiveness of existing gene-drive strains to block Plasmodium transmission, thereby reducing vector competence and minimizing the opportunities for selection of resistant parasites. Two compound effector gene modules, TP24 and TP43, were introduced using Cas9 endonuclease and dual guide RNAs into TP13-based gene-drive strains to produce the An. gambiae AgTP24 and AgTP43 strains. The gene-drive cassettes were then introgressed into An. coluzzii to produce AcTP24 and AcTP43. Gene-drive dynamics, gene conversion, and inheritance were high in all strains, with 95% to 100% inheritance of the gene-drive constructs. Life table analyses showed mixed impacts on fitness dependent on the species and copy number (hemi- or homozygosity) of the gene-drive systems. The compound effector molecule gene complexes significantly reduced both parasite prevalence and infection intensities in An. gambiae and An. coluzzii following challenge assays with the human malaria parasite, P. falciparum. These findings highlight the potential of compound effector strategies in gene-drive systems to achieve durable malaria transmission control.
Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
35363Yun Jiaqi, Ma Qin, Wang Guandong, et al., Laboratory Animal and Comparative Medicine, 45:773-783. 2026-01-14 12:01:39.
Mosquito-borne diseases (such as malaria, dengue fever, Zika virus disease, and Chikungunya) pose major threats to global public health, while traditional control methods based on chemical pesticides face severe challenges including enhanced drug resistance in vector mosquitoes and environmental pollution. Genetic control strategies have become high-potential alternative solutions for mosquito control due to their species specificity and environmental friendliness. Gene drive technology uses gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) to enable specific genes to efficiently spread in target mosquito populations through "super-Mendelian inheritance", offering a revolutionary strategy for the prevention and control of mosquito-borne diseases. This review systematically summarizes key advances, core challenges, and response strategies of gene drive technology in this field. Research advances: (1) In Anopheles malaria vectors, population suppression drives targeting sex determination genes or female reproductive genes can cause female sterility or skewed sex ratios to achieve population suppression. Population replacement gene drive strategies targeting host genes associated with Plasmodium infection or delivering anti-Plasmodium effector molecules in Anopheles can effectively block pathogen transmission. (2) In Aedes mosquito vectors of arboviruses, targeting female flight-essential genes achieves population suppression, and coupling of antiviral effector systems with drive elements is explored. Optimized split gene drive strategies demonstrate high cutting and recombination efficiency, and models predict safe and controllable spread of disease-resistance traits. (3) In Culex mosquitoes transmitting lymphatic filariasis, homology drive elements are integrated into two genes involved in the eye pigment synthesis pathway, allowing clear visualization of gene drive efficiency through eye color. Core Challenges: technological challenges include low homologous recombination repair efficiency, non-homologous end joining repair causing resistance allele generation, CRISPR/Cas9 off-target effects, and species adaptation differences. Ecological and safety challenges involve gene pool pollution caused by accidental spread of drive elements, potential ecological balance impacts, and long-term irreversible risks. Response strategies and prospects: employing multiplex guide RNA (gRNA) targeting strategies to enhance drive stability and combat potential resistance. Developing reversible designs such as synthetic resistance, reversal drives, and immunizing reversal drives as "genetic brakes". Establishing long-term ecological monitoring systems and mathematical modeling for risk assessment. Exploring "environmentally responsive drives" to enhance controllability. Future research should continuously optimize drive efficiency and specificity, deepen ecological risk evaluation, strengthen international cooperation, and promote ethical consensus and regulatory framework construction, with the aim of making gene drive technology a sustainable prevention and control strategy to address the global health challenge of mosquito-borne diseases under the premise of safety and controllability.
The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae
35269Pei-Shi Yen, Sebald A N R Verkuijl, Paolo Capriotti, et al., G3 Genes|Genomes|Genetics, 2025-11-02 17:38:52.
The modification of mosquito populations at scale through CRISPR-Cas9-mediated homing gene drives is a promising route for malaria vector control. Integral gene drives (IGDs) are designed to utilise the regulatory sequences of endogenous genes to reduce the size of the modification required for nuclease and effector expression. In this study, we describe the creation and characterisation of the nanosd IGD, which targets and is inserted into the nanos gene of the malaria vector Anopheles gambiae, and show that it achieves high rates of gene drive (98.4% in females, 99.5% in males). We find that homozygous nanosd females but not males show impaired fecundity and exhibit variable degrees of ovary underdevelopment. Transcriptomic analysis of ovaries points to decreased transcript levels of the nanos gene when harbouring Cas9 and changes to other fertility-related genes. As a minimal genetic modification, nanosd does not induce widespread transcriptomic perturbations that would affect vector competence, and we show that its susceptibility to Plasmodium spp. and O’nyong nyong virus infection remains similar to wild-type mosquitoes. Importantly, we find that nanosd propagates efficiently in caged mosquito populations and is maintained as a source of Cas9 after the emergence of drive-resistant alleles, whilst also mobilising a non-autonomous antiparasitic effector modification. The nanosd gene drive shows promise as a genetic tool for malaria vector control via population modification, and we outline steps towards its further optimisation.
The buzz stops here
35057Bill Gates, Gates Notes, 2025-08-19 20:44:24.
I've been working on malaria for over two decades. I’ve talked with researchers in labs and parents who’ve lost children to a mosquito bite. I’ve seen promising new tools and surprising setbacks. But I’ve rarely been as excited about a new innovation as I am about this one. In a lab in Tanzania, researchers are studying something incredible: a mosquito that can’t give you malaria. It looks and behaves like any other mosquito. It flies, bites, and breeds. But what it doesn’t do is transmit one of the deadliest diseases on the planet—which means it could save hundreds of thousands of lives a year. This mosquito was developed in 2023 by a team of African scientists at the Ifakara Health Institute in partnership with Imperial College London. It’s the first transgenic mosquito ever created on African soil—meaning that scientists have made a small, targeted change to its DNA. It was both a major scientific milestone and a major moment of African leadership in the global health space. The project is called Transmission Zero, and its goal is as ambitious as its name: to eliminate malaria not by killing mosquitoes, but by making them unable to transmit it to humans.
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.
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.
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.
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.
How genetically engineered mice could stop the spread of Lyme disease
33874Cristela Guerra and Stephanie Brown, WBUR Radio Boston, 2024-12-10 16:36:59.
New England has some of the highest rates of Lyme disease in the country. MIT researchers are trying to fight the disease in a project that involves releasing hundreds of thousands of engineered mice onto the shores of Nantucket and Martha's Vineyard. On Radio Boston, Kevin Esvelt, an associate professor at the MIT Media Lab and the inventor of CRISPR-based gene drive, discusses the project.
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.
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.
A model-informed target product profile for population modification gene drives for malaria control
31339Agastya Mondal, Héctor M. Sánchez C., John M. Marshall, medRxiv, 2024-09-03 18:44:21.
As reductions in malaria transmission in sub-Saharan Africa stagnate, gene drive-modified mosquitoes represent one of the most promising novel tools for continued disease control. In order to advance from the laboratory to the field, gene drives will be assessed against target product profiles, planning tools that list minimum criteria products should satisfy as they progress through the development pipeline. Here, we use an eco-epidemiological model to investigate parameter values for population modification gene drives that satisfy two previously-discussed target outcomes: a 50% reduction in clinical malaria incidence for a duration (window-of-protection) of at least three years, and a time-to-impact of less than one year. We consider two African settings, Burkina Faso and Kenya, where gene drive mosquitoes are currently being researched, and consider three transmission intensities at each. For the gene drive product, we explore rates of homing and resistance allele generation, fitness costs associated with gene drive and non-functional resistance alleles, and the efficacy of the effector gene(s) at reducing mosquito-to-human transmission. We find that when the window-of-protection criterion is satisfied, the time-to-impact criterion also is. Target outcomes are most influenced by the fitness cost associated with the gene drive allele and effector gene efficacy. Resistance allele parameters are also highly influential on target outcomes, and determine how long the gene drive allele persists in the population after most available wild-type alleles have been cleaved. Low rates of functional resistance allele generation are preferred, while costly non-functional resistance alleles will allow the drive allele to outcompete them. Homing rates already achieved for Anopheles gene drives do not need to be improved upon. A conundrum exists whereby the most important product parameters for predicting field efficacy are those that can only be reliably measured in the field, which presents a challenge for assessment of product readiness.
Advancements and Future Prospects of CRISPR-Cas-Based Population Replacement Strategies in Insect Pest Management
31330Zhao Y, Li L, Wei L, Wang Y, Han Z., Insects, 15. 2024-09-03 18:39:10.
Many insects are categorized as agricultural pests due to their ability to transmit diseases and damage crops, which results in significant economic losses. Scientists have proposed two main pest control strategies: population suppression, aimed at reducing the size or distribution of pest populations, and population replacement, which involves introducing genetically modified populations to replace wild pests after an initial release. Typically, population replacement strategies use gene drive systems to spread beneficial traits throughout the target population. Current promising gene drive systems include homing endonuclease genes (HEGs), Wolbachia, maternal-effect dominant embryonic arrest (Medea), and newly adapted CRISPR/Cas genome editing systems. This review provides an overview of the recent advancements in population replacement, including insights into the development, testing, and safe implementation of CRISPR-Cas-based gene drive techniques from laboratory settings to field applications. It also discusses recent developments, identifies research gaps, and offers a comprehensive analysis of genetic control strategies for insect pests.
Curing mosquitoes with genetic approaches for malaria control
30356Mary Kefi, Victor Cardoso-Jaime, Sally A. Saab, George Dimopoulos, Trends in Parasitology, 2024-05-21 19:48:52.
Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in ‘curing’ Anopheles vectors of the malaria parasite.
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.
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.
A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance
28651Jingheng Chen, Shibo Hou, Ruobing Feng, Xuejiao Xu, Nan Liang, Jackson Champer, bioRxiv, 2023-12-05 10:59:48.
CRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading desired genes throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we created a homing drive targeting the essential but haplosufficient hairy gene. Our strategy involves spreading the drive construct through the homing process, eliminating nonfunctional resistance, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version of hairy. This strategy eliminates resistance more slowly than a previous strategy targeting haplolethal genes, but it may be easier to construct in non-model organisms. Our drive inheritance rate was moderate, and multigenerational cage studies showed quick drive spread to 96-97% of the population. However, the drive failed to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs, a strategy that previously was successful at preventing functional resistance. Sequencing showed that these alleles had a large deletion and must have utilized an alternate start codon. The resistance allele had a modest fitness advantage over the drive in a cage study, which could prevent long-term persistence of the drive, especially if cargo genes had an additional fitness cost. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs.
Manipulating the Destiny of Wild Populations Using CRISPR
28626Raban R, Marshall JM, Hay BA, Akbari OS., Annual Reviews, 57:361-390. 2023-12-04 09:57:57.
Genetic biocontrol aims to suppress or modify populations of species to protect public health, agriculture, and biodiversity. Advancements in genome engineering technologies have fueled a surge in research in this field, with one gene editing technology, CRISPR, leading the charge. This review focuses on the current state of CRISPR technologies for genetic biocontrol of pests and highlights the progress and ongoing challenges of using these approaches.
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.
Aedes aegypti microbiome composition covaries with the density of Wolbachia infection
28495Jane Pascar, Henry Middleton & Steve Dorus, Microbiome, 11. 2023-11-17 12:21:31.
Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome.
Meiotic drive, postzygotic isolation, and the Snowball Effect
28418Robert L. Unckless, bioRxiv, 2023-11-14 12:43:39.
As populations diverge, they accumulate incompatibilities which reduce gene flow and facilitate the formation of new species. Simple models suggest that the genes that cause Dobzhansky-Muller incompatibilities should accumulate at least as fast as the square of the number of substitutions between taxa, the so-called snowball effect. We show, however, that in the special but possibly common case in which hybrid sterility is due primarily to cryptic meiotic (gametic) drive, the number of genes that cause postzygotic isolation may increase nearly linearly with the number of substitutions between species.
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.
Biotechnological Potential of Microorganisms for Mosquito Population Control and Reduction in Vector Competence
28272R. D. Katak, A. M. Cintra, B. C. Burini, O. Marinotti, J. A. Souza-Neto and E. M. Rocha, Insects, 14. 2023-10-30 07:59:35.
Mosquitoes transmit pathogens that cause human diseases such as malaria, dengue fever, chikungunya, yellow fever, Zika fever, and filariasis. Biotechnological approaches using microorganisms have a significant potential to control mosquito populations and reduce their vector competence, making them alternatives to synthetic insecticides. Ongoing research has identified many microorganisms that can be used effectively to control mosquito populations and disease transmission. However, the successful implementation of these newly proposed approaches requires a thorough understanding of the multipronged microorganism-mosquito-;pathogen-environment interactions. Although much has been achieved in discovering new entomopathogenic microorganisms, antipathogen compounds, and their mechanisms of action, only a few have been turned into viable products for mosquito control. There is a discrepancy between the number of microorganisms with the potential for the development of new insecticides and/or antipathogen products and the actual available products, highlighting the need for investments in the intersection of basic research and biotechnology.
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.
Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops
28220A. Kormos, G. Dimopoulos, E. Bier, G. C. Lanzaro, J. M. Marshall and A. A. James, Frontiers in Bioengineering and Biotechnology, 11. 2023-10-26 14:54:57.
The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.
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
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?
The Gamble: Can Genetically Modified Mosquitoes End Disease?
27985S. Nolen, New York Times, 2023-09-29 08:00:43.
The malaria situation in São Tomé and Príncipe, an African island nation with a population of 200,000, epitomizes the current challenge in the global struggle against the disease. The country is among the world’s least developed, and it has depended on foreign aid to fight malaria. Various campaigns over the past 50 years drove cases down, only to have them resurge worse than ever when the benefactor moved on. Over the past 18 years, with nearly $21 million from the Global Fund to Fight AIDS, Tuberculosis and Malaria, São Tomé has used a package of tools — including insecticide-treated bed nets; new and better drugs; killing larvae in bodies of water; and indoor spraying of homes — to stunning effect. No one has died of malaria here in the past five years. These countries need a way to fight the disease that is permanent and does not require continuous investment. Greg Lanzaro, a molecular geneticist at the University of California, Davis, who leads the malaria team, believes his grouphas that solution. “We’ve been working on this for 30 years, and from the beginning we said, ‘It has to work, but it also has to be inexpensive,and it has to be sustainable,’” he said as he watched the mosquitoes being released in a Santo Antonio park. “And we believewe have it.” But genetic modification is a controversial endeavor. Governments are hesitant, and few in Africa have laws to regulate theuse of the technology. Its risks lie in the unknowns: Could the modified mosquito evolve in some way that has harmfuleffects on the rest of the ecosystem? Could it prompt a dangerous mutation in the malaria parasite, which will find a new way to spread to survive? It is, in essence, the Jurassic Park question: Could meddling in genetic code have catastrophic consequences that no oneanticipates?
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.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti
27839Reitmayer, Christine M. Levitt, Emily Basu, Sanjay Atkinson, Barry Fragkoudis, Rennos Merits, Andres Lumley, Sarah Larner, Will Diaz, Adriana V. Rooney, Sara Thomas, Callum J. E. von Wyschetzki, Katharina Rausalu, Kai Alphey, Luk, Proceedings of the National Academy of Sciences, 120:e2303080120. 2023-09-12 09:18:45.
Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1?nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.
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.
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.
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.
Mosquitoes spread malaria. These researchers want them to fight it instead
26948G. Brumfiel, NPR, 2023-07-20 08:45:44.
Mosquitoes carry malaria, which kills hundreds of thousands of people each year. Now some researchers are trying to use genetic engineering to make the pesky insects into allies in the fight against the disease. The approach is a radical departure from traditional ways of controlling malaria. For years, public health officials have tried to limit the disease by controlling mosquito populations. But that approach is temporary, says Anthony James, a professor of molecular biology and genetics at the University of California, Irvine. Because mosquitoes are extremely tough little insects, and their populations can quickly rebound. "To try to get rid of them, I don't think it's possible," he says. Instead, James and his colleagues want to try a different approach: making mosquitoes themselves into malaria-fighting warriors.
Mosquito-friendly gene drive may lead to a malaria-free future
26945Anonymous, LIFE TECHNOLOGY, 2023-07-19 08:23:51.
A gene drive is a genetic mechanism that allows a particular gene to spread rapidly through a population. In the case of malaria, scientists are working on developing a gene drive that would make mosquitoes resistant to the parasite that causes the disease. This would reduce the number of mosquitoes that can transmit the disease to humans. However, there are concerns about the use of gene drives. One potential issue is that the gene drive could spread beyond the intended population of mosquitoes and affect other species. Another concern is that the gene drive could have unintended consequences, such as creating new diseases or disrupting ecosystems. To address these concerns, scientists are developing a new type of gene drive that is "mosquito-friendly." This means that the gene drive would only affect mosquitoes that carry the malaria parasite, rather than all mosquitoes. This would reduce the risk of unintended consequences and help to ensure that the gene drive is effective in reducing the spread of malaria.
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
26580R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James, Proceedings of the National Academy of Sciences, 120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
Mosquitoes made immune to malaria could help stamp out the disease
26614C. Wilson, NewScientist, 2023-07-10 13:29:44.
Mosquitoes have been gene edited so they are immune to the parasites that cause malaria. If released into the wild, the genetic modification should spread through a population of mosquitoes because it contains a sequence known as a “gene drive”, which means all the modified insects’ offspring would inherit the immunity. This approach could slash the numbers of malaria cases in people. Malaria is one of the world’s leading causes of death and ill health, taking a particular toll on young children in sub-Saharan Africa. Two vaccines have recently been developed, but they only give partial immunity. Other high-tech strategies against mosquito-borne diseases are under investigation, including gene drives that kill all mosquitoes in a targeted area. But these could have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
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.
MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito population
26616C. H. Sánchez, D. L. Smith and J. M. Marshall, bioRxiv, 2023-06-23 13:35:51.
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible - ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii)an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is freely available as an open-source Python package on pypi ( https://pypi.org/project/MGSurvE/ ). It is intended as a resource for both field and computational researchers interested in mosquito gene surveillance. AUTHOR SUMMARY: Mosquito-borne diseases such as malaria and dengue fever continue to pose a major health burden throughout much of the world. The impact of currently-available tools, such as insecticides and antimalarial drugs, is stagnating, and gene drive-modified mosquitoes are considered a novel tool that could contribute to continuing reductions in disease transmission. Gene drive approaches are unique in the field of vector control in that they involve transgenes that could potentially spread on a wide scale, and consequently, surveillance is expected to be a major cost driver for the technology. This is needed to monitor for unintended spread of intact drive alleles, and the emergence of alternative alleles such as homing-resistance alleles and non-functional effector genes. Additionally, surveillance of insecticide-resistance alleles is of interest to support the impact of insecticide-based tools such as bednets. Here, we present MGSurvE, a computational framework that optimizes trap placement for genetic surveillance of mosquito populations in order to minimize the time to detection for an allele of interest. MGSurvE has been tailored to various features of mosquito ecology, and is intended as a resource for researchers to optimize the efficiency of limited surveillance resources.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
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.
Mosquito gene targeted RNAi studies for vector control
25650M. Yadav, N. Dahiya and N. Sehrawat, Functional and Integrative Genomics, 23:180. 2023-05-25 07:55:21.
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
25098N. de Graeff, I. Pirson, R. van der Graaf, A. L. Bredenoord and K. R. Jongsma, Bioethics, 2023-05-03 10:11:03.
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
Mathematical modeling of the performance of wild and transgenic mosquitoes in malaria transmission
25861A. P. Wyse, A. J. B. dos Santos, J. D. Azevedo, A. C. de Meneses and V. M. D. Santos, Plos One, 18:23. 2023-04-28 08:20:19.
A mathematical model that simulates malaria transmission under the influence of transgenic mosquitoes refractory to malaria is presented in this paper. The zygosity of transgenic mosquitoes is taken into account and, consequently, the total population of mosquitoes is comprised of wild type and heterozygous and homozygous transgenic mosquitoes. These three mosquito varieties interact by mating and competition, and the genetic characteristics of their resulting offspring are in accordance with Mendelian genetics or the mutagenic chain reaction (MCR) technique. Although the incorporation of transgenic mosquitoes into the ecosystem reduces the incidence of malaria, the model also takes into account the importance of completing treatment in individuals with confirmed infection and the imminent risk of increased environmental temperature.
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.
Modelling the effect of migration on the localisation and spread of a gene drive
24955C. Benjamin James and F.-L. Alexandre Jules Hen, bioRxiv, 2023.04.02.535303. 2023-04-04 14:22:19.
Gene drives have the potential to address pressing ecological issues. Through the super-Mendelian inheritance of a gene drive, a trait can be spread through a population even in spite of a fitness cost. This ability to spread is both its greatest quality and detractor. We may not want a gene drive to spread universally. If a gene drive were designed to cause the collapse of a pest population, it may inadvertently cause the collapse of the entire species. Migration is the mechanism through which a gene drive can spread to distant populations. Understanding its effect on the progression of a gene drive is crucial to our ability to control a gene drive. While migration can spread the gene drive to other populations, equally it can bring in other alleles to the population that may disrupt the progression of the gene drive. Through our deterministic migration gene drive model we can assess the conditions in which a gene drive is likely to spread to unintended populations, and if a gene drive is likely to be displaced by incoming alleles.Competing Interest StatementThe authors have declared no competing interest.
First transgenic mosquito made in Africa by Transmission Zero
24962H. Dunning, Imperial College London, 2023-04-04 10:33:04.
Transmission Zero, a global scientific programme led by scientists at Imperial College London and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), announces the generation of the first transgenic mosquito strain ever to be made in Africa.This strain carries in its genome genetic modifications that will allow scientists in the future to render mosquitoes unable to transmit malaria. This major scientific achievement is a pivotal milestone in the renewed international efforts to rid Africa of malaria. Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through mosquito bites. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa.
The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination
24901S. James and M. Santos, Tropical Medicine and Infectious Disease, 2023-03-29 07:50:09.
Malaria remains an ongoing public health challenge, with over 600,000 deaths in 2021, of which approximately 96% occurred in Africa. Despite concerted efforts, the goal of global malaria elimination has stalled in recent years. This has resulted in widespread calls for new control methods. Genetic biocontrol approaches, including those focused on gene-drive-modified mosquitoes (GDMMs), aim to prevent malaria transmission by either reducing the population size of malaria transmitting mosquitoes or making the mosquitoes less competent to transmit the malaria parasite. The development of both strategies has advanced considerably in recent years, with successful field trials of several biocontrol methods employing live mosquito products and demonstration of the efficacy of GDMMs in insectary-based studies. Live mosquito biocontrol products aim to achieve area-wide control with characteristics that differ substantially from current insecticide-based vector control methods, resulting in some different considerations for approval and implementation. The successful field application of current biocontrol technologies against other pests provides evidence for the promise of these approaches and insights into the development pathway for new malaria control agents. The status of technical development as well as current thinking on the implementation requirements for genetic biocontrol approaches are reviewed, and remaining challenges for public health application in malaria prevention are discussed.
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.
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.
Hybrid incompatibilities in the anopheles gambiae species complex
24968A. Kriezis, Imperial College London, 2023-03-01 10:47:20.
Malaria is an infectious disease caused by parasites of the genus Plasmodium which is responsible for approximately 400,000 deaths annually, primarily in sub-Saharan Africa. Malaria is transmitted by mosquitoes belonging to the Anopheles gambiae species complex. While progress has been made to reduce the incidence of malaria, the emergence of insecticide resistance necessitates the development of novel vector control strategies. Gene drive technologies have seen significant advances in recent years, providing hope for their implementation in the near future. While gene flow has been identified between sibling species of the An. gambiae species complex, they are reproductively isolated by both pre- and post-zygotic isolation mechanisms. Interspecific crosses between most member species produce sterile hybrid males, in accordance with Haldane’s rule of speciation. The aim of this project was to support the development of gene drive technologies by investigating hybrid incompatibilities between two of the most significant vector species, Anopheles gambiae and Anopheles arabiensis. The potential for the introgression of genomic regions from one species into the genetic background of the other was investigated to help inform models regarding the spread of gene drives between sibling species. In addition, the identification of genetic elements involved in hybrid male sterility could provide potential targets for vector control strategies. Large autosomal regions were found to introgress and persist in interspecific genomes without a detectable fertility cost. In addition, the introduction of distinct autosomal regions of conspecific DNA into otherwise heterospecific genomes of hybrid males was found to overcome hybrid incompatibilities and partially restore fertility. While no specific genetic factors involved in hybrid incompatibilities could be identified, the results indicate that such factors are present at least on the X chromosome. Furthermore, the evidence suggests that asynapsis between interspecific homologous autosomes during gametogenesis plays a role in the manifestation of hybrid male sterility.
Gene Drive Technology With Agricultural Application Potential
24788R. Carmeli-Peslak, SeedWorld, 2023-02-22 09:51:36.
Gene drive technology, a genetic phenomenon that occurs in nature, causes a trait to spread in species through sexual reproduction over many generations. The inheritance rate is higher than the Mendelian rate which is 50%. Gene drives have been used for public health and conservation, but can potentially be used in multiple species, like agricultural pests according to a release. Weeds and pests have a negative impact on crops and their impact has caused interest in potentially using genetic techniques, like gene drive, to help control weeds and pests. Current insect pest control includes the use of pesticides which has helped to decrease food loss and waste. Research around new tools will help continue to protect crops and reduce food waste while also minimizing agriculture’s environmental footprint. These new tools and practices include gene editing techniques. Now in its early stages, gene-drive-based strategies are being research to help reduce agricultural pests. The gene-drive-based strategies will focus on both controlling pests that cause damage and spreading desired crop or livestock traits faster. A limitation with this strategy is that gene drives cannot work on asexually reproducing organisms. The strategy is also unsuitable for species that have longer generation times. While gene-drive-based strategies may not meet all the needs, but it is a helpful tool to continue to investigate.
Biopolitik: The Promise of Gene Drive
24708S. Todi, Technopolitik, 2023-02-07 09:57:49.
Gene drives are genetic elements of an organism that are transmitted to progeny at higher than mendelian frequencies (>50%). Gene editing techniques such as CRISPR–Cas9 have made gene drives extremely efficient in laboratory settings and have shown the potential to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. Research in gene drives, especially on mosquitoes, is being carried out by scientists at the University of California, San Diego, Texas A&M University, and Massachusetts Institute of Technology, among others. However, concerns have been raised regarding the potential unintended consequences, especially in terms of the ecological impact of gene-drive systems.
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.
A Zika virus-responsive sensor-effector system in Aedes aegypti
24699S. Basu, C. M. Reitmayer, S. Lumley, B. Atkinson, M. L. Schade-Weskott, S. Rooney, W. Larner, E. E. Montiel, R. Gutierrez-Lopez, E. Levitt, H. M. Munyanduki, A. M. E. Elrefaey, A. T. Clarke, S. Koit, E. Zusinaite, R. Fragkoudis, A. Merits and L. Alphey, bioRxiv, 2023.02.06.527261. 2023-02-06 12:38:46.
Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted primarily through the bite of an infected mosquito, Aedes aegypti being the main vector. ZIKV infection is associated with a range of adverse effects; infection during pregnancy can lead to foetal abnormalities, including microcephaly. Lacking a licensed vaccine, or specific therapeutics, control of ZIKV transmission focuses on vector control. However, in most transmission settings, current methods are insufficient to successfully control ZIKV, or other similarly-transmitted arboviruses such as dengue and chikungunya viruses. This has stimulated interest in genetics-based methods, either to reduce the number of mosquitoes (population suppression), or to make mosquitoes less able to transmit (population modification). Here, we describe a method to selectively eliminate infected mosquitoes, using a virus sensor inserted into the mosquito genome and coupled to a quorum-counting lethal effector. In mosquitoes, ZIKV normally establishes persistent, lifelong infection; survival of these infected mosquitoes is crucial to transmission potential. Correspondingly, removal of infected mosquitoes can reduce vectorial capacity of a mosquito population, i.e. ability to transmit. Since relatively few mosquitoes become infected, typically <2%, engineered hypersensitivity to ZIKV would have only a modest population-level fitness cost, and lower still if transmission were successfully reduced by such means.Competing Interest StatementThe authors have declared no competing interest.
Ethical dilemma: Should we get rid of mosquitoes?
24650Talya Hackett, TED-Ed, 2023-01-30 09:59:15.
Mosquitoes are responsible for more human deaths every year than any other animal, but very few of the 3,500 mosquito species actually transmit deadly diseases to humans. Scientists have been conducting experiments using engineered technologies called gene drives that could theoretically get rid of the most lethal mosquitoes. So, should we eradicate these pesky insects? Talya Hackett investigates.
Engineered Antiviral Sensor Targets Infected Mosquitoes
24617E. Dalla Benetta, A. J. Lopez-Denman, H.-H. Li, R. A. Masri, D. J. Brogan, M. Bui, T. Yang, M. Li, M. Dunn, M. J. Klein, S. Jackson, K. Catalan, K. R. Blasdell, P. Tng, I. Antoshechkin, L. S. Alphey, P. N. Paradkar and O. Akbari, bioRxiv, 2023.01.27.525922. 2023-01-27 09:22:47.
Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. We engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR Cas13 and its potent collateral activity. Akin to a stealthy Trojan Horse hiding in stealth awaiting the presence of its enemy, REAPER remains concealed within the mosquito until an infectious blood meal is up taken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13 mediated RNA targeting significantly reduces viral replication and its promiscuous collateral activity can even kill infected mosquitoes. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.Competing Interest StatementO.S.A is a founder of both Agragene, Inc. and Synvect, Inc. with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. L.A is an adviser to Synvect, Inc and Biocentis Ltd., with financial interest in each. All other authors declare no competing interests.
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.
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.
Gene Drives Could Fight Malaria and Other Global Killers but Might Have Unintended Consequences
24460M. Cobb, Scientific American, 2023-01-13 08:22:55.
Every year more than 600,000 people die from mosquito-transmitted malaria, most of them children under age five. Some insects that are disease vectors, such as mosquitoes, are currently expanding their range around the world, bringing new threats. Genetic engineering can fix this by permanently altering insect genes through what is known as a gene drive. This technology allows a chosen set of genes to alter an animal’s biology in some way, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the laws of inheritance. The genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, their careful use might save millions of lives by making mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for a such a techno fix.
Tolerance-conferring defensive symbionts and the evolution of parasite virulence
24126C. A. Smith and B. Ashby, bioRxiv, 2022-12-05 09:03:54.
Defensive symbionts in the host microbiome can confer protection from infection or reduce the harms of being infected by a parasite. Defensive symbionts are therefore promising agents of biocontrol that could be used to control or ameliorate the impact of infectious diseases. Previous theory has shown how symbionts can evolve along the parasitism-mutualism continuum to confer greater or lesser protection to their hosts, and in turn how hosts may coevolve with their symbionts to potentially form a mutualistic relationship. However, the consequences of introducing a defensive symbiont for parasite evolution and how the symbiont may coevolve with the parasite have yet to be explored theoretically. Here, we investigate the ecological and evolutionary implications of introducing a tolerance-conferring defensive symbiont into an established host-parasite system. We show that while the defensive symbiont may initially have a positive impact on the host population, parasite and symbiont evolution tend to have a net negative effect on the host population in the long-term. This is because the introduction of the defensive symbiont always selects for an increase in parasite virulence and may cause diversification into high- and low-virulence strains. Even if the symbiont experiences selection for greater host protection, this simply increases selection for virulence in the parasite, resulting in a net negative effect on the host population. Our results therefore suggest that tolerance-conferring defensive symbionts may be poor biocontrol agents for population-level infectious disease control.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.
Research: Scientists Modify Mosquitoes That Can’t Spread Malaria
23775N. Kharbanda, Onlymyhealth, 2022-10-07 07:00:18.
According to a research, scientists have found a way to genetically engineer mosquitoes with the capability to slow down the multiplication of malaria-causing parasites in their gut. This is an advance study, that can help in preventing the infecting of the disease in humans. The disease spreads in people because of a female mosquito when it bites someone infected with the malaria parasite. The parasite grows into the next stage in the mosquito’s gut and transports to its salivary glands, to infect the next human it bites. These modified mosquitoes produce compounds which interfere in the growth of malaria-causing parasites, which are then not able to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects are dead. The team of researchers from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation have created a model which can analyse the effect of such changes if used in various African settings. They also found that the modification of these mosquitoes could be helpful even in locations where the transmission rate is high.
Explained: How Scientists Are Genetically modifying Mosquitoes To Reduce Malaria
23772Anonymous, Outlook, 2022-10-07 06:57:17.
he Delhi High Court on Friday asked the state government to inform it within two weeks of the proposal of increasing the fine amount in mosquito breeding cases. The court last year took suo moto cognizance of the issue of large-scale mosquito breeding in the city, resulting in the spread of vector-borne diseases With a sudden increase in malaria cases across the country, a recent research might provide some respite. Scientists have genetically modified mosquitoes to slow the growth of malaria-causing parasites in their guts — an advancement that can help prevent transmission of the disease to humans. Though only around 10 per cent of mosquitoes live long enough for the infectious parasite to develop, malaria remains one of the most devastating diseases globally, putting at risk about half of the world’s population. In 2021, it infected 241 million people and killed 627,000 people.
Explained: How scientists engineered mosquitoes that cannot spread malaria
23670FP Explainers, Firstpost, 2022-10-06 08:14:50.
The world of science is reaching new heights. Scientists have now developed mosquitoes that will bite you but not cause malaria. The study was conducted by a team of researchers called Transmission: Zero at the Imperial College of London. The results of the research were published in the Science Advances journal. Genetically modified mosquitoes have the ability to slow the growth of malaria-causing parasites in their gut, an innovation that can help prevent transmission of the disease to humans. Owing to the devastating effects of Malaria, which is putting about half of the world’s population at risk, scientists came up with this new method in the hope to deter the growth of the parasite.
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.
Malaria-free mosquito engineered by scientists
23697GNA, MODERN GHANA, 2022-10-03 07:54:35.
Scientists have genetically modified the main malaria-carrying species of mosquito in sub-SaharanAfrica to slow the growth of malaria-causing parasites in their gut, preventing transmission of thedisease to humans. When the Anopheles gambiae takes a blood meal, it produces two molecules called antimicrobialpeptides in its guts, according to the scientists. These peptides, which were originally isolated from honeybees and African clawed frogs, impair themalaria parasite's development. Now researchers from the Transmission Zero team at Imperial College London have come up with adesign that can be combined with existing “gene drive” technology to spread the modification anddrastically cut malaria transmission. Collaborators from the Institute for Disease Modelling at the Bill and Melinda Gates Foundation,which funded the research, also developed a model that, for the first time, can assess the impact ofsuch modifications if used in a variety of African settings. They found that the modification developed by the Imperial team could be a powerful tool forbringing down cases of malaria even where transmission is high.
Scientists stunt parasite growth to tackle malaria
23769RSS24.news, RSS24.NEWS, 2022-09-29 06:52:01.
Loss of life, loss of livlihoods and homelessness have already afflicted these flood marooned refugees in Pakistan. Now these living conditions means they also face sickness and and without protection malaria is a major threat. Health agencies try to protect people against infection with sprays, nets and a vaccine for children, there are also preventative medicines. But despite all these, there were 241 million cases of malaria in 2020 and an estimated 627,000 deaths according to the latest malaria report from the World Health Organization (WHO). The WHO says these strategies, which are also used for other mosquito borne diseases such as Zika and dengue, are only partially effective. In the meantime the insects are becoming inceasingly resistant to insecticides. Scientists have for many years been investigating whether they can control the life cycle of mosquitoes by manipulating their DNA, thereby creating genetically modified mosquitoes. The disease is spread by a parasite Plasmodium falciparum which grows and reaches maturation inside the female Anopheles mosquito.
Scientists are manipulating the DNA of mosquitoes to fight the spread of malaria
23766R. Min, EURONEWS.NEXT, 2022-09-29 06:48:00.
Scientists say they have managed to genetically modify mosquitoes so that they are unable to spread malaria, a disease that kills well over half a million people each year. The changes cause mosquitoes to live shorter lives, while the parasites inside them, which cause the fatal infection, develop more slowly. This slashes the chances of mosquitoes living long enough to carry fully grown parasites – and transmit the disease to the humans they bite.Malaria is spread by the parasite Plasmodium falciparum, which grows and reaches maturation inside the female Anopheles mosquito. The average mosquito survives on average seven to 10 days in the wild. "By prolonging the developmental time that the parasite needs inside the mosquito to become infectious, this 10 per cent becomes now much smaller".
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.
Scientists engineer mosquitoes that cannot spread malaria
23601J. Dalton, Independen, 2022-09-22 14:30:39.
Scientists have engineered mosquitoes that cannot give humans malaria, saying their work could potentially eliminate the disease. Researchers at Imperial College London genetically modified the insects so that the growth of malaria-causing parasites in their guts was slowed.
Scientists Engineer Mosquitoes That Can’t Transmit Malaria
23598C. Murez, US News, 2022-09-22 14:21:57.
The fight against malaria could hinge on genetically engineered mosquitoes that have something called "gene drive."Researchers from the Transmission: Zero team at Imperial College London report that they have engineered mosquitoes that slow the growth in their gut of the parasites that cause malaria. This delay would mean the mosquito would reach its natural life span before the parasite would reach the mosquitoes' salivary glands. So a bite wouldn't spread the disease. In the lab, this dramatically reduced the spread of malaria. "Since 2015, the progress in tackling malaria has stalled. Mosquitoes and the parasites they carry are becoming resistant to available interventions such as insecticides and treatments, and funding has plateaued. We need to develop innovative new tools," study co-author Tibebu Habtewold said in a college news release. He's a researcher from the college's Department of Life Sciences. Last year, malaria infected 241 million people, killing 627,000 of them, mostly children younger than age 5 in sub-Saharan Africa.
Mosquitoes that can’t spread malaria engineered by scientists
235842022-09-22 14:04:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing 'gene drive' technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Scientists engineer mosquitoes that can’t spread malaria
23581S. Varshney, Gamacher Central, 2022-09-22 13:58:18.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.
Mosquitoes with honeybee DNA could tame malaria
23579R. Blakely, The Times, 2022-09-22 13:53:23.
A new form of genetically engineered mosquito could reduce the spread of malaria in Africa, a study suggests. The addition of DNA from a honeybee and genetic material from the African clawed frog prompt the new mosquitoes to produce compounds to stunt the growth of the parasite that causes malaria. This means that the parasite, and therefore the disease, is less likely to be passed on to human victims via mosquito bite. To be useful in the real world this would have to be coupled with an existing technology known as a gene drive, a controversial genetic tool that would force the new characteristic through populations of mosquitoes as they reproduce. For malaria to spread, a female mosquito must bite someone infected with the malaria
Genetically Engineered Mosquitoes Prevented the Growth of Malaria-causing Parasites in Their Gut
23576P. Mozter, Nature World News 2022, 2022-09-22 13:45:51.
Abstract: Scientists have created mosquitoes that inhibit the development of malaria-causing parasites in their stomachs, therefore decreasing disease transmission to people. The genetic change allows mosquitoes to create substances in their intestines that inhibit parasite development, making parasites less likely to reach the mosquitoes' salivary glands and be transmitted in a bite before the insects die, as per ScienceDaily. The Transmission: Zero team at Imperial College London developed the breakthrough so that it may be used with current "gene drive" technologies to distribute the alteration and substantially reduce malaria transmission. The team is planning field experiments, but first, they will rigorously verify the new modification's safety before merging it with a gene drive for real-world testing.
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.
Mosquitoes are being genetically modified so they can’t spread malaria
23596M. Le Page, New Scientist, 2022-09-21 14:17:06.
Gene editing mosquitoes so they die before malaria parasites can develop inside them could stop the spread of the deadly parasite entirely,
Genetically-modified mosquitoes could ‘help wipe out malaria’
23594S. Knapton, The Telegraph, 2022-09-21 14:11:56.
Mosquitoes that cannot spread malaria have been genetically engineered by British scientists, in a breakthrough that could help eliminate the disease. ...
Scientists engineer mosquitoes that can’t spread malaria
23572Imperial College London, Phys Org, 2022-09-21 13:32:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria. The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing "gene drive" technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Extreme GM “extinction technology” of gene drives presented as “natural”
23625GM Watch, GM Watch, 2022-09-19 14:45:48.
Now similar Orwellian moves are happening in the area of gene drives. A gene drive is a genetic engineering technology that forces a particular genetic modification through a population by changing the natural rules of inheritance, usually to ensure that it is increasingly – or always – inherited. Gene drive organisms are built to intentionally spread their engineered traits through an entire population, turning on its head the usual imperative to try to contain and prevent engineered genes from contaminating and disrupting ecosystems. They can be designed to re-model or delete entire species. Gene drive technology is deeply unpopular and rightly feared by the public and regulators. It is against this background that in recent years, some researchers have begun to describe so-called "selfish genetic elements" found in nature* as "natural gene drives" and to present gene drive as a "ubiquitous natural phenomenon".
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.
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.
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.”
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.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
23307S. Leung, N. Windbichler, E. A. Wenger, C. A. Bever and P. Selvaraj, Malaria Journal, 21:226. 2022-07-26 07:49:07.
BACKGROUND: Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa. METHODS: Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated. Various transmission regimes (low, moderate, and high-corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated. RESULTS: Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80-90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80-90%. CONCLUSION: A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.
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.
A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes
23150E. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois, bioRxiv, 2022.07.08.499187. 2022-07-08 09:32:53.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild type Lipophorin, causing the anti-malarial modified Lipophorin version to hitch-hike together with the Saglin drive. Although producing drive-resistant alleles, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to affect parasite transmission by two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.Competing Interest StatementThe authors have declared no competing interest.
The Florida Keys Mosquito Control District & Oxitec Announce Launch of Next Phase of Ground-Breaking Project
23093Oxitec, Oxitec, 2022-06-30 07:38:27.
In a continuation of the FKMCD-Oxitec Mosquito Project, Oxitec and FKMCD announced that a new phase of the project (“Pilot D”) will be initiated on or after July 7th, 2022. This phase of the project will examine single-point releases of Oxitec’s male mosquitoes. In March of this year the EPA granted an extension of the Experimental Use Permit (EUP) for the continuation of this pilot project. Following this national-level approval, the Florida Department of Agriculture and Consumer Services (FDACS), reviewed and approved Oxitec’s state-level permit applications. The 2022 project launched with Pilot B during the week of May 9th, with the placement of Oxitec’s just-add-water mosquito boxes on private property of volunteer residents in three release areas, all on Vaca Key. Untreated comparison sites are monitored with mosquito traps on Key Colony Beach and Vaca Key.
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.
Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae
22689D. A. Ellis, G. Avraam, A. Hoermann, C. A. S. Wyer, Y. X. Ong, G. K. Christophides and N. Windbichler, PLOS Genetics, 18:e1010244. 2022-06-02 14:26:57.
Author summary Gene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations.
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.
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.
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.
MIT Researchers Propose Using Genetically Modified Mice to Fight Lyme Disease
21917K. Perrotte, Field and Stream, 2022-04-25 08:49:40.
In Massachusetts, researchers at MIT are proposing an experiment that would involve releasing genetically engineered mice into the native mouse population to ultimately reduce the prevalence of Lyme disease.Nantucket Island is the area proposed for the study, which has been years in development. Martha’s Vineyard is also under consideration. Researchers hope to find out if they can break the transmission cycle between ticks and white-footed mice—the primary carriers of Lyme disease. Ticks typically become carriers of the Lyme bacterium by biting infected mice, and then they pass it on to other mice as well as humans. Reductions in the number of infected ticks should, therefore, result in reduced human infections, according to the theory.
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.
UC Davis — Malaria Gene Drive Feasibility Analysis
21563Good Ventures, Good Ventures, 2022-03-31 12:24:36.
Open Philanthropy recommended a grant of $10,248,967 over three years to UC Davis to support subsequent stages of a feasibility analysis of a potential test of gene drives for malaria control on the adjoining West African islands of São Tomé and Príncipe. The work, led by Dr. Greg Lanzaro and colleagues, will focus on a potential gene drive application that would reduce or inhibit the ability of mosquitoes to transmit the malarial parasite, without impacting the size of the mosquito population on the islands. As part of the preliminary feasibility analysis, which Open Philanthropy supported in February 2020, Dr. Lanzaro’s team developed working relationships with local communities, established an ethics advisory board, developed a communication plan, and conducted appropriate safety tests.
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.
A UC malaria initiative program receives grant for work researching genetically engineered mosquitoes
20483S. Slater, The California Aggie, 2022-02-23 08:39:35.
Malaria, a mosquito-borne infectious disease, was discovered in 1880, and has remained widespread in tropical regions around the equator including parts of Africa, Asia and Latin America, resulting in thousands of deaths and a significant blow to economic development in these regions. Many of the attempted strategies to eliminate malaria in the past have planned to do so by eliminating mosquitoes entirely — but according to a recent press release, the Vector Genetics Laboratory (VGL) at UC Davis, in collaboration with a UC malaria initiative program that originally started at UC Irvine, and with the financial support of a $10.2 million grant from Open Philanthropy, is taking a different approach. “Mosquitoes are a part of the ecosystem,” Greg Lanzaro, project principal investigator and director at VGL, said. “Our strategy does not eliminate mosquitoes. The mosquitoes will still be there, they’ll just be incapable of transmitting malaria. In every sense these mosquitoes are normal mosquitoes, except for the fact that they can’t transmit malaria.” The idea is called a “population modification strategy,” Lanzaro said, explaining that groups at UC Irvine and Johns Hopkins University genetically engineered mosquitoes that are incapable of transmitting the malaria parasite. “The way that malaria is transmitted is that the mosquito bites a person who has malaria and it picks up the parasite in the blood that it feeds on,” Lanzaro said. “Then the parasite develops in the mosquito so that when the mosquito bites the next person, they spread the parasite. Our mosquitoes have been engineered with a couple of genes that kill the parasite inside of the mosquito, so they’re not able to transmit.”
Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development
20447A. Hoermann, T. Habtewold, P. Selvaraj, G. Del Corsano, P. Capriotti, M. G. Inghilterra, K. M. Temesgen, G. K. Christophides and N. Windbichler, bioRxiv, 2022.02.15.480588. 2022-02-17 09:41:11.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of endemic settings.Competing Interest StatementThe authors have declared no competing interest.
C-type lectin 4 regulates broad-spectrum melanization-based refractoriness to malaria parasites
20489M. L. Simões, Y. Dong, G. Mlambo and G. Dimopoulos, PLOS Biology, 20:e3001515. 2022-02-13 08:53:42.
Anopheles gambiae melanization-based refractoriness to the human malaria parasite Plasmodium falciparum has rarely been observed in either laboratory or natural conditions, in contrast to the rodent model malaria parasite Plasmodium berghei that can become completely melanized by a TEP1 complement-like system-dependent mechanism. Multiple studies have shown that the rodent parasite evades this defense by recruiting the C-type lectins CTL4 and CTLMA2, while permissiveness to the human malaria parasite was not affected by partial depletion of these factors by RNAi silencing. Using CRISPR/Cas9-based CTL4 knockout, we show that A. gambiae can mount melanization-based refractoriness to the human malaria parasite, which is independent of the TEP1 complement-like system and the major anti-Plasmodium immune pathway Imd. Our study indicates a hierarchical specificity in the control of Plasmodium melanization and proves CTL4 as an essential host factor for P. falciparum transmission and one of the most potent mosquito-encoded malaria transmission-blocking targets.
Scientists find transmission chain-breaker, give new hope for fight against malaria
20473ANI, ANI, 2022-01-27 08:09:19.
A recent study, published online in 'PLoS Biology', has revealed that blocking a key protein found in Anopheles gambiae mosquitoes -- the principal vector for malaria transmission to humans in Africa could thwart infection with malaria parasites and thus prevent them from transmitting the parasites to humans. The study was undertaken by Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. In a lab experiment, the researchers used CRISPR/Cas9 gene-editing technology to delete the gene for a protein called CTL4 from Anopheles gambiae mosquitoes. This deletion made the mosquitoes highly resistant to the malaria parasite. The researchers found that disrupting the CTL4 protein brought a 64 percent decrease in infection prevalence. The researchers believe that targeting the CTL4 protein could be the basis for new strategies to control malaria in regions where it is still endemic.
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.
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.
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.
Genomic insertion locus and Cas9 expression in the germline affect CRISPR/Cas9-based gene drive performance in the yellow fever mosquito Aedes aegypti
19603W. R. Reid, J. Lin, A. E. Williams, R. Juncu, K. E. Olson and A. W. E. Franz, bioRxiv, 2021.12.08.471839. 2021-12-08 18:56:04.
The yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive systems. Here we report an autonomous single-component gene drive system in Ae. aegypti that is designed for persistent population replacement. Critical to the design of a single-locus autonomous gene drive is that the selected genomic locus be amenable to both gene drive and the appropriate expression of the antiviral effector. In our study, we took a reverse engineering approach to target two genomic loci ideal for the expression of antiviral effectors and further investigated the use of three promoters for Cas9 expression (nanos, β2-tubulin, or zpg) for the gene drive. We found that both promoter selection and genomic target site strongly influenced the efficiency of the drive, resulting in 100% inheritance in some crosses. We also observed the formation of inheritable gene drive blocking indels (GDBI) in the genomic locus with the highest levels of gene drive. Overall, our drive system forms a platform for the further testing of driving antipathogen effector genes through Ae. aegypti populations.Competing Interest StatementThe authors have declared no competing interest.
Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila
19441G. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 118:e2107413118. 2021-12-01 20:58:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. As a consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-ClvRdbe are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli.
High-resolution in situ analysis of Cas9 germline transcript distributions in gene-drive Anopheles mosquitoes
19324G. Terradas, A. Hermann, A. A. James, W. McGinnis and E. Bier, G3-Genes Genomes Genetics, 2021-11-15 14:20:36.
Gene drives are programmable genetic elements that can spread beneficial traits into wild populations to aid in vector-borne pathogen control. Two different drives have been developed for population modification of mosquito vectors. The Reckh drive (vasa-Cas9) in Anopheles stephensi displays efficient allelic conversion through males but generates frequent drive-resistant mutant alleles when passed through females. In contrast, the AgNosCd-1 drive (nos-Cas9) in Anopheles gambiae achieves almost complete allelic conversion through both genders. Here, we examined the subcellular localization of RNA transcripts in the mosquito germline. In both transgenic lines, Cas9 is strictly coexpressed with endogenous genes in stem and premeiotic cells of the testes, where both drives display highly efficient conversion. However, we observed distinct colocalization patterns for the two drives in female reproductive tissues. These studies suggest potential determinants underlying efficient drive through the female germline. We also evaluated expression patterns of alternative germline genes for future gene-drive designs.
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.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modeling study
19134S. Leung, N. Windbichler, E. Wenger, C. Bever and P. Selvaraj, bioRxiv, 2021.11.01.466856. 2021-11-03 14:42:23.
Genetically engineering mosquitoes is a promising new vector control strategy to reinvigorate the fight against malaria in Sub-Saharan Africa. Using an agent-based model of malaria transmission with vector genetics, we examine the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission and quantify the gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting. We evaluate the performance of two different gene drive systems: "classic" and "integral". Various transmission regimes (low, moderate, and high - corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare seeking, are also simulated. Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above approximately 80-90‰). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as approximately 50‰ and in high transmission regimes with transmission-blocking effectiveness values above approximately 80-90‰. Thus, a single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.Competing Interest StatementThe authors have declared no competing interest.
Modeling the efficacy of CRISPR gene drive for schistosomiasis control
19109R. E. Grewelle, J. Perez-Saez, J. Tycko, E. K. O. Namigai, C. G. Rickards and G. A. De Leo, bioRxiv, 2021.10.29.466423. 2021-11-01 14:51:40.
CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. While much effort has been spent developing gene drives in mosquitoes, gene drive technology in molluscs has received little attention despite the role of freshwater snails as obligate, intermediate hosts of parasitic flukes causing schistosomiasis -- a disease of poverty affecting more than 200 million people worldwide. A successful drive in snails must overcome self-fertilization, which prevents a drive's spread. Simultaneous hermaphroditism is a feature of snails -- distinct from gene drive model organisms -- and is not yet incorporated in gene drive models of disease control. Here we developed a novel population genetic model accounting for snails' sexual and asexual reproduction, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We then integrated this model with an epidemiological model of schistosomiasis transmission and snail population dynamics. Simulations showed that gene drive establishment can be hindered by a variety of biological and ecological factors, including selfing. However, our model suggests that, under a range of conditions, gene drive mediated immunity in snails could maintain rapid disease reduction achieved by annual chemotherapy treatment of the human population, leading to long-term elimination. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and close evaluation of the genetic and ecological landscape.Competing Interest StatementJT and EKON were seed funded by the Merck Innovation Cup 2016 for research on schistosomiasis, and previously employed as external consultants to the Global Health Institute of Merck (KGaA) which produces treatments for schistosomiasis. REG and GADL were partially supported by the National Science Foundation's grants DEB-2011179 and ICER-2024383.
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.
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.
Spatial modelling for population replacement of mosquito vectors at continental scale
18861N. J. Beeton, A. Wilkins, A. Ickowicz, K. R. Hayes and G. R. Hosack, bioRxiv, 2021.10.06.463299. 2021-10-06 18:41:08.
We explore transmission of the gene drive between the subspecies, different hybridisation mechanisms, the effects of both local dispersal and potential wind-aided migration to the spread, and the development of resistance to the gene drive. We find that given best current available knowledge on the subspecies’ life histories, an introduced gene drive system with typical characteristics can plausibly spread from even distant offshore islands to the African mainland with the aid of wind-driven migration, with resistance taking over within a decade. Our model demonstrates a range of realistic dynamics including the effect of prevailing wind on spread and spatio-temporally varying carrying capacities for subspecies. We thus show both the plausibility and importance of accounting for a wide range of mechanisms from regional to continental scales
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.
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.
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.
Mosquito transgenesis for malaria control
18284S. Dong, Y. Dong, M. L. Simões and G. Dimopoulos, Trends in Parasitology, 2021-09-02 14:42:32.
Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies.
Identifying Sites for Testing Modified Mosquitoes as a Strategy to Eradicate Malaria
18222A. Fell, UC Davis News, 2021-08-18 15:34:12.
In a newly published article in the journal Evolutionary Applications Professor Greg Lanzaro and his team at the Vector Genetics Laboratory, UC Davis School of Veterinary Medicine, set forth a framework for the selection of field sites in Africa best suited for testing genetically engineered mosquitoes (GEMs).“We followed earlier recommendations from the National Academy of Sciences and the World Health Organization that argued that a physical island would be a logical place to initiate early field trials of a GEM that uses gene drive technology,” Lanzaro said.n this paper, they establish a set of criteria including geographic and genetic isolation, biological complexity, island size, and topography and apply these criteria to a set of 22 potential island sites located off the coast of Africa. Their goal is to identify sites that maximize prospects for success, minimize risk, and serve as a fair, valid and convincing test of the efficacy and impacts of a GEM product intended for large-scale deployment in Africa.
Gene drives gaining speed
17972E. Bier, Nature Reviews Genetics, 2021-08-06 13:50:56.
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
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.
Using gene drives to control malaria
17594A. Fell, Daily News, 2021-06-25 14:08:33.
A group of UC scientists led by Greg Lanzaro, professor of pathology, microbiology and immunology in the UC Davis School of Veterinary Medicine, recently completed an analysis of a strategy aimed at eliminating malaria from Africa using genetically engineered mosquitoes. Lanzaro’s lab is part of the UC Irvine Malaria Initiative. The laboratories of Anthony James at UC Irvine and Ethan Bier at UC San Diego engineered mosquitoes with synthetic genes that render them incapable of transmitting the malaria parasite and coupled these genes with a CRISPR-Cas9 gene drive to promote their spread into malaria vector populations in Africa. The idea is to ‘drive’ the new malaria-resistance genes into the mosquito population at a much higher rate than could occur naturally.
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%.
Population modification strategies for malaria vector control are uniquely resilient to observed levels of gene drive resistance alleles
17502G. C. Lanzaro, H. M. Sánchez C, T. C. Collier, J. M. Marshall and A. A. James, BioEssays, 2021-06-20 13:46:45.
Cas9/guide RNA (gRNA)-based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite-refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinction. DNA sequence polymorphisms representing alternate alleles at gRNA target sites may confer a drive-resistant phenotype in individuals carrying them. Modeling predicts that, for observed levels of SGV at potential target sites and observed rates of de novo DRA formation, population modification strategies are uniquely resilient to DRAs. We conclude that gene drives can succeed when fitness costs incurred by drive-carrying mosquitoes are low enough to prevent strong positive selection for DRAs produced de novo or as part of the SGV and that population modification strategies are less prone to failure due to drive resistance.
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
The origin of island populations of the African malaria mosquito, Anopheles coluzzii
17287M. Campos, M. Hanemaaijer, H. Gripkey, T. C. Collier, Y. S. Lee, A. J. Cornel, J. Pinto, D. Ayala, H. Rompao and G. C. Lanzaro, Communications Biology, 4:9. 2021-05-26 10:26:11.
Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome study of 142 specimens from nine countries in continental Africa and three islands in the Gulf of Guinea. This sample set covers a large part of this species' geographic range. Our population genomic analyses included a description of the structure of mainland populations, island populations, and connectivity between them. Three genetic clusters are identified among mainland populations and genetic distances (F-ST) fits an isolation-by-distance model. Genomic analyses are applied to estimate the demographic history and ancestry for each island. Taken together with the unique biogeography and history of human occupation for each island, they present a coherent explanation underlying levels of genetic isolation between mainland and island populations. We discuss the relationship of our findings to the suitability of Sao Tome and Principe islands as candidate sites for potential field trials of genetic-based malaria control strategies. Campos, Lanzaro and colleagues use whole-genome sequencing and population genomic analyses to infer connectivity between mainland and island mosquito populations in West Africa. The unique biogeographic history for each island population is reported, and the findings highlight potential candidate sites for genetic-based malaria control strategies.
Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective?
18710Z. N. Adelman and B. B. Kojin, Journal of Medical Entomology, 58:1997-2005. 2021-05-21 13:50:24.
Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission. Additionally, many approaches, while effective against the parasite, also disrupt or alter important aspects of mosquito physiology, leading to corresponding changes in lifespan, reproduction, and immunity. As the most promising approaches move towards field-based evaluation, questions of effector gene robustness and durability move to the forefront. In this forum piece, we critically evaluate past effector gene approaches with an eye towards developing a deeper pipeline to augment the current best candidates.
Targeting conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
17054M. Walter, R. Perrone and E. Verdin, Journal of virology, 2021-05-19 13:32:53.
Here, we analyze in cell culture experiments the evolution of resistance in a viral gene drive against human cytomegalovirus. We report that, after an initial invasion of the wildtype population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionary conserved sequences ensures that drive-resistant viruses acquire long-lasting mutations and are durably attenuated. As a consequence, and even though engineered viruses do not stably persist in the viral population, remaining viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in herpesviruses, especially for therapeutic applications.<b>Importance</b>The use of defective viruses that interfere with the replication of their infectious parent after co-infecting the same cells - a therapeutic strategy known as viral interference - has recently generated a lot of interest. The CRISPR-based system that we recently reported in herpesviruses represents a novel interfering strategy that causes the conversion of wildtype viruses into new recombinant viruses and drives the native viral population to extinction. In this report, we analyzed how targeted viruses evolved resistance against the technology. Through numerical simulations and cell culture experiments with human cytomegalovirus, we show that, after the initial propagation, a resistant viral population is positively selected and outcompetes engineered viruses over time. We show however that targeting evolutionary conserved sequences ensures that resistant viruses are mutated and attenuated, which leads to a long-term reduction of viral levels. This marks an important step toward the development of novel therapeutic strategies against herpesviruses.
Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive
16932G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee, bioRxiv, 2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.
CRISPR may help curb malaria by altering a mosquito’s gut genes, new study suggests
16828Cornell Alliance for Science, Genetic Literacy Project, 2021-04-21 16:46:24.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife. The study is the latest in a series of steps toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Mosquito are becoming increasingly resistance to insecticides and malaria parasites are gaining resistance to antimalarial drugs, creating an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach to controlling mosquitoes, locusts and other insects. They work by creating genetically modified mosquitoes that, when released into the environment, mate with wild insects. The offspring contain genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite. But scientists must prove that this approach is safe and effective before releasing gene drive mosquitoes into the wild.
Eliminating malaria via a simple genetic modification
16822S. Gunn, Front Line Genomics, 2021-04-20 16:32:44.
Despite decades worth of research and efforts, data from 2015 onwards suggests that there has been no significant progress in reducing global malaria cases. Every year, around 400,00 people die from malaria, with over 90% of cases being within sub-Saharan Africa. The rise of mosquito resistance to pesticides as well as malaria parasite resistance to antimalarial drugs has emphasised the urgent need for the development of new tools to fight this disease. One approach that researchers are exploring is the use of gene drives. A gene drive is a genetic modification that can spread through a population at higher inheritance rates than normal. In this context, researchers can genetically modify mosquitos that, when released into the environment, would spread genes to either reduce mosquito populations or make them less likely to spread the malaria parasite. Due to concerns regarding the safety of gene drives, it is vital that researchers prove that this approach is safe and effective before releasing the modified mosquitos into the wild. There are currently no clear pathways for safely testing these tools within endemic countries.
This Malaria Preventing Mosquito Is Not A GMO But Is A Science Boost For Nature – Will Activists Want To Block It?
16816H. Campbell, science 2.0, 2021-04-20 16:13:03.
Mosquitoes like Aedes aegypti don't have any value ecologically. If Thanos snapped them out of existence tomorrow there is nothing they do that won't immediately be taken up by 3,000 other mosquito species, not to mention 25,000 bee species when it comes to pollination. The only thing they are great at is killing people; by being a leading source of vector-borne dengue disease. Not far behind is Anopheles gambiae mosquitoes, which carry malaria. Malaria kills nearly as many people each year as COVID-19 did in 2020 but there is no Warp Speed program to keep poor people in developing nations from dying. Environmental activists (overwhelmingly white and wealthy) instead spend $2 billion a year scaring people of color in other countries about science. Pesticides wiped out malaria in the U.S.(1) and remain the best way to go. DDT still works well and is in common use in afflicted countries.(2) Though banned politically in the U.S. half a century ago, our EPA literally writes the manual for how to spray it in homes elsewhere, but the Rachel Carson dream was to replace pesticides with genetically modified crops - optimizing nature to keep other parts of nature from killing everything using fewer chemicals.
Breeding Malaria Out: Scientists Engineer Mosquitos to Spread Antimalaria Genes
16800L. Papadopoulos, INTERSTING ENGINEERING, 2021-04-17 13:57:17.
According to the Centers for Disease Control and Prevention (CDC), malaria is a "serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans." There are four types of malaria parasites: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae with P. falciparum being the one most likely to result in death. But what if these mosquitos could be genetically altered to spread antimalaria genes instead of the disease? That would be nothing short of a miracle. Researchers from Imperial College London have successfully altered a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species. This innovation may result in curbing malaria once and for all. This is especially important as the parasite that causes malaria has been becoming increasingly resistant to antimalarial drugs.
Curbing Malaria’s Spread by Genetic Engineering
16792Anonymous, Genetic Engineering & Biotechnology News, 2021-04-15 13:03:49.
There is an urgent need to find new ways to combat the growing mosquito resistance to pesticides and malaria parasite resistance to antimalarial drugs. Gene drives are being tested as a new approach. In a new study, researchers from the Imperial College London reported that their approach brings gene drives one step closer as a potential strategy for eliminating malaria. Their study was published in the journal eLife, in a paper titled, “Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement.”
New genetic modification could cut malaria spread
16789Staff Writers, MALAYSIA NOW, 2021-04-15 12:56:54.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife on Tuesday. The study is the latest in a series of steps being taken toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Growing mosquito resistance to pesticides, as well as malaria parasite resistance to antimalarial drugs, has created an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach. They work by creating genetically modified mosquitoes that, when released into the environment, would spread genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite.
Researchers Using Mutant Mosquitoes To End Malaria, Which Kills 4 Lakh Per Year
16797M. Mohanti, India Times, 2021-04-14 13:20:52.
Every year, more than 22 crore people get infected with malaria and more than 4 lakh die because of it. In fact, in 2019, nearly half of the world's population was at risk of malaria. According to WHO, infants or children aged under 5 years are the most vulnerable group, accounting for two-third of all malaria deaths worldwide. Malaria is caused by parasites that are transmitted to people via the bites of infected female Anopheles mozzies. In a non-immune individual, symptoms--fever, headache, and chills--usually appear 10–15 days after the infective mosquito bite. If it goes untreated for a day, these mild symptoms can progress to severe illness, often leading to death, if bitten by the P. falciparum parasite.
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.
Current Effector and Gene-Drive Developments to Engineer Arbovirus-Resistant Aedes aegypti (Diptera: Culicidae) for a Sustainable Population Replacement Strategy in the Field
16596W. R. Reid, K. E. Olson and A. W. E. Franz, J Med Entomol, 2021-03-12 20:35:28.
Conventional mosquito control efforts based on insecticide treatments and/or the use of bednets and window curtains are currently insufficient to reduce arbovirus prevalence in affected regions. Novel, genetic strategies that are being developed involve the genetic manipulation of mosquitoes for population reduction and population replacement purposes. Population replacement aims at replacing arbovirus-susceptible wild-type mosquitoes in a target region with those that carry a laboratory-engineered antiviral effector to interrupt arboviral transmission in the field.
Genetically modified mosquitoes for better health
16527D. Devis, COSMOS, 2021-03-04 18:24:41.
One method of preventing these mosquito-born diseases is to use insecticides to kill the mozzies and remove them, but sometimes this only works as a short term solution, or has unintended devasting effects on the ecosystem. Another method for decreasing the number of disease-carrying mozzies is to introduce disease resistant, genetically modified mozzies. These transgenic mozzies could be part of a gene drive system where they have a newly introduced disease-resistant gene, linked up with CRISPR mechanisms that help the gene dominate in the population by continuing to copy itself through the genome. All of this requires very thorough risk assessment.
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
16530G. R. Hosack, A. Ickowicz and K. R. Hayes, Royal Society Open Science, 8:201525. 2021-03-03 18:28:51.
The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
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.
Exploring Gene Drive Technologies in Agriculture, Biodiversity and Human Disease
15963The GBIRd Partnership and The GeneConvene Global Collaborative, Gene Drive Research Forum, 2021-01-14 21:37:12.
The GBIRd Partnership and The GeneConvene Global Collaborative recently collaborated through The Gene Drive Research Forum, to create and produce an engaging conversation between Drs. Fred Gould and Charles Godfray about gene drive technologies – the potential benefits and complicating factors for agriculture, biodiversity, and human disease.
CRISPR and the splice to survive: New gene-editing technology could be used to save species from extinction—or to eliminate them.
16011E. Kolbert, New Yorker, 2021-01-11 14:25:59.
About a year ago, not long before the pandemic began, I paid a visit to the center, which is an hour southwest of Melbourne. The draw was an experiment on a species of giant toad known familiarly as the cane toad. The toad was introduced to Australia as an agent of pest control, but it promptly got out of control itself, producing an ecological disaster. Researchers at the A.C.D.P. were hoping to put the toad back in the bottle, as it were, using crispr.
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.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
Control of malaria-transmitting mosquitoes using gene drives
15693T. Nolan, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190803. 2020-12-28 15:31:23.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
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.
Mosquito population modification: the drive to malaria eradication
15272A. A. James, BugBitten BMC, 2020-11-27 14:37:56.
We have had considerable success in the past demonstrating that we can use modern molecular biological and insect transgenesis tools to make genes that prevent mosquitoes from passing on parasites (see 1 and 2). We have focused most recently on laboratory experiments to find ways to move these genes into wild mosquito populations.
ARRIGE 2020 Meeting | The promise of CRISPR and gene drive systems to end malaria in Africa
15145E. Gomez-Diaz, ARRIGE org, 2020-11-16 17:08:32.
Presentation by Elena Gómez Díaz (IPBLN-CSIC, Granada, Spain) at the ARRIGE 2020 meeting on "The promise of CRISPR and gene drive systems to end malaria in Africa". Discussion is included at the end of the Ruud de Maagd presentation.https://youtu.be/te3MJ8EZoes
Brave New Planet: Reshaping Nature Through Gene Drives
15047E. Lander, Brave New Planet, 2020-11-09 19:26:24.
A new technology, called gene drives, has the power to spread any genetic instructions you wish across an entire animal or plant species in the wild. It might let us restore ecosystems ravaged by invasive species, or help species adapt to climate change. And, it might save millions of children from dying of malaria. But could altering nature in this way, and on this scale, have unintended consequences? And, when it comes reshaping ecosystems, who needs to say yes?
Gene drive blocks malaria transmission in mosquitoes
15035labonline, labonline, 2020-11-09 15:46:59.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites. Their work has been published in the journal Nature Communications.
Gene Drives: A Controversial Tool to Fight Malaria
15008H. Albert, LABIOTECH.eu, 2020-11-09 15:41:52.
The possibility of creating gene drives was introduced into the scientific community in 2003 by Austin Burt, a professor at Imperial College London. Burt was studying ‘selfish genes’ that can copy themselves into a specific target DNA sequence. He suggested that these genes, called homing endonucleases, could be used to make the majority of an organism’s offspring inherit a specific gene, instead of only half of it. This technology has a lot of potential. For example, it could be used to decimate populations of malaria-carrying mosquitoes by making the majority of their offspring male. However, there are concerns about the permanent nature of these genetic modifications and whether it could cause irreparable damage to the ecosystem it is used in.
A gene-drive rescue system for the modification of malaria mosquito populations
14901A. Adolfi, Nature Research Bioengineering Community, 2020-11-03 18:48:29.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes
14898UCI, UCI News, 2020-11-03 14:11:01.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects to survive or reproduce,” said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at the Tata Institute for Genetics and Society. “While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis and arboviral diseases.”
GeneConvene Global Collaborative Webinar Series | Gene Drive Technical Webinars
14347David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2020-10-12 02:54:40.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.
Risks of releasing gene drives mosquitoes – a possible future scenario
15143Testbiotech, 2020-09-17 17:01:45.
Genetically engineering the genome of an organism with gene drive means that it will be replicated in every following generation. This allows the altered gene to spread rapidly throughout natural populations, which may be decimated or even eradicated. The video contains both factual and fictional content (the latter marked as „possible future scenario“). The fictional content shows the possible future consequences of using gene drive technology - and is intended to stimulate broad public debate. Civil society needs to engage intensively with issues around new developments in the field of biotechnology and genetic engineering.
A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population
14387J. Champer, E. Yang, E. Lee, J. Liu, A. G. Clark and P. W. Messer, Proceedings of the National Academy of Sciences, 202004373. 2020-09-14 15:23:07.
Here, we present a CRISPR homing drive that was able to successfully spread to all individuals in a laboratory cage study in Drosophila melanogaster without any apparent evolution of resistance.
Anthony James / Mosquito Modification
14229Big Picture Science, SETI Institute, 2020-08-24 20:26:09.
Anthony James, vector biologist at the University of California, Irvine, describeshow we might genetically modify mosquitoes to make them unable to pass malaria on to humans.
Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae
14015R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James, Proceedings of the National Academy of Sciences, 202010214. 2020-08-24 12:38:12.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
Engineered Reproductively Isolated Species Drive Reversible Population Replacement
13837A. Buchman, I. Shriner, T. Yang, J. Liu, I. Antoshechkin, J. M. Marshall, M. W. Perry and O. S. Akbari, bioRxiv, 2020.08.09.242982. 2020-08-10 15:42:26.
Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. We engineer multiple reproductively isolated SPECIES and demonstrate their threshold-dependent gene drive capabilities in D. melanogaster.
Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi
13593A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James, bioRxiv, 2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.
ENSSER | Gene Drive Webinar Series
12568European Network of Scientists for Social and Environmental Responsibility, 2020-06-16 20:50:52.
This series of five Webinars by some of the authors of the interdisciplinary Gene Drive Report (2019) and were organised by four organisations of independent scientists: the European Network of Scientists for Social and Environmental Responsibility (ENSSER), Critical Scientists Switzerland (CSS), Vereinigung Deutscher Wissenschaftler (VDW), Sciences Citoyennes (SC). The series was aimed at a lay audience and were intended to address these questions. Does it really work? Is it being applied? What problems do gene drives address? What side effects can they have? Who has an interest in this? Should we do it? Are gene drives regulated by law? Are they a wise solution to these problems? Who decides?
Mosquitoes engineered to resist the malaria parasite
12440Anonymous, Lab+Life Scientist, 2020-06-07 20:22:39.
Anopheles mosquitoes that have been genetically engineered with multiple antimalaria molecules, acting at different stages of the malaria life cycle, are strongly resistant to the parasite that causes malaria and are unlikely to lose that resistance quickly.
New study highlights success of gene drive technology with preventing mosquito-spread diseases
12401A. Meckler-Pacheco, The California Aggie, 2020-05-25 18:47:25.
For the past 30 years, researchers have studied the usage of gene drive technology to stop the spread of malaria. The idea is to create genetically engineered mosquitoes (GEM) that are either resistant to carrying the malaria parasite or that fail to reproduce, which would result in the reduction of the mosquito population. The gene drive technology relies on the use of the Cas-9 enzyme, which ensures the passing of the new modified genes onto offspring in the introduced population.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
11465A. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020-05-10 15:19:12.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression.
Gene editing and the war against malaria
11226E. Bier and E. Sobber, American Scientist, 102:162. 2020-04-16 15:34:38.
Malaria is a devastating disease transmitted from person to person by mosquitoes. It kills more than 400,000 people per year, more than half of those deaths being children 5 years old or younger. CRISPR (clustered regularly interspaced short palindromic repeats) is a new gene-editing technology that acts like a pair of molecular scissors: It is used to “cut and paste” DNA sequences to alter gene function. In “Gene Editing and the War Against Malaria” (pages 162–169), Ethan Bier and Elliott Sober describe how biologists can now alter genes in a malaria-transmitting mosquito population by engineering a CRISPR gene drive, which mimics a natural evolutionary process. With this tool, a new gene can be inserted into the genome so that the alteration is rapidly passed down to successive sexually reproducing generations. Two gene-drive strategies have been found feasible: The first drives a local malaria-transmitting population to extinction; the second renders mosquitoes unable to transmit malaria, which breaks the malaria transmission cycle.
Engineering a minimal gene drive system for integral replacement in Drosophila melanogaster
25648A. Nash, Imperial College London, 2020-04-01 07:48:50.
Gene drives represent a powerful tool for the control of vector-borne diseases. By suppressing or replacing vector populations, laboratory studies have highlighted the potential for this group of tools to make a powerful impact on the burden of zoonotic disease. Current genetic drive systems have a number of limitations, namely their complexity, susceptibility to genetic resistance, and a high regulatory threshold. Here we suggest a novel design paradigm for the creation of replacement gene drives, which we have termed ‘Integral Replacement’. By splitting drive constructs, and integrating components into endogenous loci, we have aimed to engineer a minimal drive system, with low fitness cost, higher resilience to resistance alleles, and with greater flexibility for field testing. In so doing we have generated a model that illustrates increases in efficacy versus existing drive systems, and expanded on work performed on intronic gRNA cassettes. We subsequently were able to build prototype Integral Gene Drive (IGD) components, and demonstrate their efficacy using the model organism Drosophila melanogaster, providing evidence for an initial proof-of-principle for this novel design paradigm.
Synthetically engineered mosquitos could neutralize dengue virus infection
6943L. Woolfe, Biotechniques, 2020-01-22 15:59:46.
Dengue virus infection can be severe and life threatening. New research has developed an improved approach to controlling this deadly infection.
Mosquitoes genetically modified to combat dengue
6740Downtoearth, Down To Earth, 2020-01-20 20:22:34.
For the first time mosquitoes have been engineered to fight all 4 known types of dengue
Genetically Modified Mosquitos Neutralize Dengue Virus
6737N. P. Dyal, Infectious Disease Advisor, 2020-01-20 18:53:09.
Researchers at the University of California San Diego have identified a target gene in mosquitos that renders the insects completely refractory to all 4 serotypes of the dengue virus and thus, incapable of transmitting the virus to humans, according to study results published in PLoS Pathogens
Genetically modified mosquitoes resist all dengue viruses, researchers find
6709B. Burton, C|NET, 2020-01-17 18:24:25.
This new kind of mosquito can't spread any form of the deadly disease.
Genetically engineered mosquitoes resist spreading any form of dengue
6734K. Servick, Science, 2020-01-16 18:50:53.
Recover from dengue once, and you’re not necessarily free and clear. The mosquito-borne disease marked by fever, rash, and debilitating pain results from any of four genetically distinct versions of the dengue virus. Previously infected people who get hit with a second of these “serotypes” can face more severe, even life-threatening symptoms. Now, by endowing a line of mosquitoes with an antibody against the virus, researchers have for the first time made insects that—at least in lab tests—appear unable to spread any form of the disease. In theory, these mosquitoes could be released into the wild to suppress the circulation of the virus.
Genetically engineered mosquitoes halt Dengue spread
6730L. Thomas, New Medical Life Sciences, 2020-01-16 18:44:27.
A new study published in the journal PLOS Pathogens in January 2020 reports the development of mosquitoes that have been genetically modified to resist infection by several types of the dengue virus. This is the first time ever that all types of the virus have been targeted by the engineering of the mosquito DNA. Covering all virus types is essential to achieve proper disease control.
Researchers Genetically Modify First Batch Of Mosquitoes Resistant To All Four Types Of Dengue
6725M. Dapcevich, IFL Science, 2020-01-16 18:39:05.
An international team of researchers have synthetically engineered a breed of mosquitos that are resistant to all four types of the dengue virus for the first time, a feat they say may someday suppress the disease and stop its transmission to humans.
Genetically engineered mosquitoes are immune to all strains of dengue virus for first time
6719G. Weule, ABC News Online, 2020-01-16 18:34:13.
Locked in a secure lab near Melbourne is the newest addition in the fight against dengue: genetically engineered mosquitoes that are resistant to all strains of the potentially deadly virus.
Mosquitoes resistant to all types of dengue virus engineered
6714N. Lavars, New Atlas, 2020-01-16 18:28:54.
Last year, scientists at Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO) made a big breakthrough, engineering mosquitoes that break the chain of Zika virus transmission. But they did so with multiple targets in mind, with the mosquito in question, Aedes aegypti, also acting as the number one disease vector for the dengue virus. The researchers have now added this arrow to the quiver of their genetically-modified mosquitoes, with hopes of tackling what they see as a global epidemic.
Broad dengue neutralization in mosquitoes expressing an engineered antibody
6706A. Buchman, S. Gamez, M. Li, I. Antoshechkin, H.-H. Li, H.-W. Wang, C.-H. Chen, M. J. Klein, J.-B. Duchemin, J. E. Crowe, Jr., P. N. Paradkar and O. S. Akbari, PLOS Pathogens, 16:e1008103. 2020-01-16 18:18:14.
Author summary With limited success of traditional vector control methods to curb dengue infections and more than half of the world’s population still at risk, there is a need for novel strategies to reduce its impact on public health. Recent advances in genetic technologies has allowed for precise modifications of mosquito genome to make them resistant to infections, thus breaking the transmission cycle. Here we generated engineered Ae. aegypti mosquitoes efficiently expressing a DENV-targeting single-chain variable fragment (scFv) derived from a previously characterized broadly neutralizing human antibody, which blocked infection and transmission in these mosquitoes. To our knowledge, this is the first example of an engineered transgene capable of rendering Ae. aegypti mosquitoes 100% refractory to all four serotypes of DENV. The engineered mosquitoes, in future, could easily be paired with a gene drive, capable of spreading the transgene throughout wild disease-transmitting mosquito populations and preventing further DENV transmission. Since a number of diverse and well-characterized antibodies exist against other arboviruses (eg chikungunya and Zika, this work also provides a proof-of-concept principle for developing similar genetic strategies for reducing the impact of these arboviruses.
Antiviral effectors and gene drive strategies for mosquito population suppression or replacement to mitigate arbovirus transmission by Aedes aegypti
6634A. E. Williams, A. W. E. Franz, W. R. Reid and K. E. Olson, Insects, 11:1-18. 2020-01-12 20:05:33.
The mosquito vector Aedes aegypti transmits arthropod-borne viruses (arboviruses) of medical importance, including Zika, dengue, and yellow fever viruses. Controlling mosquito populations remains the method of choice to prevent disease transmission. Novel mosquito control strategies based on genetically manipulating mosquitoes are being developed as additional tools to combat arbovirus transmission. Genetic control of mosquitoes includes two basic strategies: population suppression and population replacement. The former aims to eliminate mosquito populations while the latter aims to replace wild populations with engineered, pathogen-resistant mosquitoes. In this review, we outline suppression strategies being applied in the field, as well as current antiviral effector genes that have been characterized and expressed in transgenic Ae. aegypti for population replacement. We discuss cutting-edge gene drive technologies that can be used to enhance the inheritance of effector genes, while highlighting the challenges and opportunities associated with gene drives. Finally, we present currently available models that can estimate mosquito release numbers and time to transgene fixation for several gene drive systems. Based on the recent advances in genetic engineering, we anticipate that antiviral transgenic Ae. aegypti exhibiting gene drive will soon emerge; however, close monitoring in simulated field conditions will be required to demonstrate the efficacy and utility of such transgenic mosquitoes.
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.
Biomphalaria glabrata Granulin Increases Resistance to Schistosoma mansoni Infection in Several Biomphalaria Species and Induces the Production of Reactive Oxygen Species by Haemocytes
13835J. R. Hambrook, A. A. Gharamah, E. A. Pila, S. Hussein and P. C. Hanington, Genes, 11:12. 2019-12-28 15:36:48.
In this study, we demonstrate that in vivo addition of Biomphalaria glabrata pro-granulin (BgGRN) can reduce Schistosoma mansoni infection success in numerous Biomphalaria sp. when challenged with different S. mansoni strains. We also demonstrate that cleavage of BgGRN into individual granulin subunits by elastase results in the stimulation of haemocytes to produce reactive oxygen species.
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives
5626Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer, bioRxiv, 861435:861435. 2019-12-17 16:38:34.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based underdominance gene drive constructs employing toxin-antidote principles. These drives disrupt the wild-type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero invasion threshold frequency, referring to the critical frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same-site” and “distant-site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR toxin-antidote underdominance drive systems could allow for the design of highly flexible and potentially confinable gene drive strategies.
Malaysia Wolbachia trials: Battling dengue and other mosquito-borne viruses
170592019-11-22 13:47:09.
Viral gene drive in herpesviruses
5917Walter, M. and E. Verdin, bioRxiv, 2019:717017. 2019-07-30 16:38:14.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.
Population modification of Anopheline species to control malaria transmission
6694R. Carballar-Lejarazú and A. A. James, Pathogens and Global Health, 111:424-435. 2018-02-01 17:58:10.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow resources to be allocated to new control sites while maintaining treated areas free of malaria. Synthetic biological approaches are being used to generate transgenic mosquitoes for population modification. Proofs-of-principle exist for mosquito transgenesis, the construction of anti-parasite effector genes and gene-drive systems for rapidly introgressing beneficial genes into wild populations. Key challenges now are to develop field-ready strains of mosquitoes that incorporate features that maximize safety and efficacy, and specify pathways from discovery to development. We propose three pathways and a framework for target product profiles that maximize safety and efficacy while meeting the demands of the complexity of malaria transmission, and the regulatory and social diversity of potential end-users and stakeholders.
A cage replacement experiment involving introduction of genes for refractoriness to Plasmodium-yoelii-nigeriensis into a population of Anopheles gambiae (Diptera, Culicidae)
6230P. M. Graves and C. F. Curtis, Journal of Medical Entomology, 19:127-133. 1982-03-24 21:46:47.
A caged population of Anopheles gambiae was allowed to breed continuously and samples of the progeny were tested for susceptibility to Plasmodium yoelii nigeriensis. Males of a strain partially refractory to this parasite were released into the population for an 18-wk period. The susceptibility of the population declined from 100% to about 50% and remained at that level for several months after releases were terminated. Separate experiments showed that the fitness of the adult males and larvae of the refractory strain was much less than that of the susceptible caged strain. The observed change in the susceptibility of the caged population was compared with the expectations on various assumptions about the relative fitness of the refractory and susceptible strains. It appears that initially the efficiency of the replacement process was considerably reduced because of poor fitness of the refractory strain. Once the refractoriness genes were in the caged population, however, they were able to recombine with the genes causing poor fitness and the latter could be eliminated by natural selection, leaving a considerable degree of refractoriness in the population. The results are discussed in relation to the possibility of vector control by the release of males from a refractory strain and with particular reference to the advantages and disadvantages of the use of a negatively heterotic system to assist the replacement process and the release of both sexes.
Transporting marker gene re (red eye) into a laboratory cage population of Aedes-aegypti (Diptera Culicidae), using meiotic drive at MD locus
6233R. J. Wood, L. M. Cook, A. Hamilton and A. Whitelaw, Journal of Medical Entomology, 14:461-464. 1977-12-24 21:51:08.
An attempt has been made to use the meiotic drive gene MD to transport a marker re (redeye) into a laboratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the laboratory. The need for field estimates of fitness is indicated.
Field trial of competitive displacement of Aedes-polynesiensis by Aedes-albopictus on a Pacific atoll
6235L. Rosen, L. E. Rozeboom, W. C. Reeves, J. Saugrain and D. J. Gubler, American Journal of Tropical Medicine and Hygiene, 25:906-913. 1976-11-01 21:53:54.
Prior laboratory studies and field observations suggested that it might be possible to reduce the size of the population of, or eliminate, Aedes polynesiensis by the introduction of Aedes albopictus. The former mosquito is the principal vector of nonperiodic filariasis caused by Wuchereria bancrofti and the latter is a closely related species refractory to the development of human filariae. The practicability of such competitive displacement was studied by a field trial on a remote coral atoll where there was an established population of A. polynesiensis. Three strains of A. albopictus were liberated at separate localities on the atoll and their fate was followed for 4 years. One strain disappeared within 12 months after release and the other two disappeared within 48 months. It was not clear whether A. albopictus failed to become established because the strains were unsuitable, the general environment was inappropriate, or A. polynesiensis was present in such numbers that A. albopictus rarely succeeded in mating with its own species.
Population replacement in Culex fatigens by means of cytoplasmic incompatibility. Laboratory experiments with non-overlapping generations
6291C. F. Curtis and T. Adak, Bulletin of the World Health Organization, 51:249-255. 1974-01-08 19:45:42.
Bidirectional cytoplasmic incompatibility in the Culex pipiens complex appears to provide a mechanism for the replacement of a wild population by a strain refractory to filaria or a strain made partly sterile by a translocation. As a preliminary test of the feasibility of the replacement process, various ratios of strains with the cytoplasm of either Delhi or Paris, which are bidirectionally incompatible, were tested in laboratory cages. Where one strain was marked with the ruby-eye gene, this strain always declined in frequency in the next generation. In experiments in which the Paris strain was marked with a male-linked translocation complex, after 2-4 generations of breeding there was complete elimination of either the Paris or the Delhi type depending, as expected, on the relative frequencies of the two types with which the population began. In one experiment a type with Paris cytoplasm devoid of the translocation was found. This type increased in frequency in succeeding generations. The possible causes of origin of this type and its relevance to the practical use of the replacement principle are discussed.
Possible replacement of malaria mosquitoes
6118S. Avery Jones, Transactions of The Royal Society of Tropical Medicine and Hygiene, 51:469-470. 1957-08-10 19:43:41.
Sir,--The purpose of this letter is to draw the attention of research workers in control of mosquito colonies to the possible value of investigating the factors governing the infection of mosquitoes with parasites of human malaria. If a strain of a vector species could be isolated that has inability to become infective as a dominant characteristic, the way would be opened up to implant such mosquitoes in areas where the normal vectors of the same species have been reduced in numbers. There is the hope that they would breed and become locally predominant.
Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org