For Researchers
Acceptability of emergent Aedes aegypti vector control methods in Ponce, Puerto Rico: A qualitative assessment
29010Pérez-Guerra CL, Rosado-Santiago C, Ramos SA, Marrero-Santos KM, González-Zeno G, Partridge SK, et al., PLoS Global Public Health, 2024-03-11 13:41:04.
Aedes aegypti control has been fraught with challenges in Puerto Rico. The government has implemented commonly used vector control methods, but arboviral epidemics still occur. It is necessary to explore new Ae. aegypti control methods. This study aimed to understand the perceptions of community members in Ponce, Puerto Rico about emergent and traditional Ae. aegypti vector control methods and determine their acceptability and support for these methods. We identified the type of information needed to increase support for emergent vector control methods, and the preferred strategies to disseminate this information. Four group discussions were conducted with a total of 32 participants representing eight of the 14 clusters participating in the Communities Organized for the Prevention of Arboviruses (COPA), a project designed to mobilize communities in Ponce, Puerto Rico to prevent diseases transmitted by mosquitoes. Group discussions began with an overview of different methods used for controlling Ae. aegypti mosquitoes. These overviews facilitated participant understanding of the mosquito control methods presented. Use of source reduction, autocidal gravid ovitraps (AGO), and manual application of larvicide for arboviral mosquito control received support from almost all participants. Vector control methods that use more familiar techniques in Puerto Rico such as truck-mounted larvicide spraying (TMLS) and insecticide residual spraying received support from most participants. More than half of participants supported the use of emergent mosquito control methods including Wolbachia suppression, Wolbachia replacement, or genetically modified mosquitoes (GMM). Participants preferred to receive vector control information through house-to-house visits with the distribution of written materials, followed by dissemination of information through traditional (i.e., radio, television) and social media. The detailed information resulting from this study was used to develop messages for a communications campaign to garner future community support. Community acceptance and support are critical for the success of vector control programs using emergent mosquito control methods.
Efficacy of Wolbachia-based mosquito control: Predictions of a spatially discrete mathematical model
29008David Dye, John W. Cain, PLoS One, 19. 2024-03-11 12:43:55.
Wolbachia is an endosymbiont bacterium present in many insect species. When Wolbachia-carrying male Aedes aegypti mosquitoes mate with non-carrier females, their embryos are not viable due to cytoplasmic incompatibility. This phenomenon has been exploited successfully for the purpose of controlling mosquito populations and the spread of mosquito-borne illnesses: Wolbachia carriers are bred and released into the environment. Because Wolbachia is not harmful to humans, this method of mosquito control is regarded as a safer alternative to pesticide spraying. In this article, we introduce a mathematical framework for exploring (i) whether a one-time release of Wolbachia carriers can elicit a sustained presence of carriers near the release site, and (ii) the extent to which spatial propagation of carriers may allow them to establish fixation in other territories. While some prior studies have formulated mosquito dispersal models using advection-reaction-diffusion PDEs, the predictive power of such models requires careful ecological mapping: advection and diffusion coefficients exhibit significant spatial dependence due to heterogeneity of resources and topography. Here, we adopt a courser-grained view, regarding the environment as a network of discrete, diffusively-coupled “habitats”—distinct zones of high mosquito density such as stagnant ponds. We extend two previously published single-habitat mosquito models to multiple habitats, and calculate rates of migration between pairs of habitats using dispersal kernels. Our primary results are quantitative estimates regarding how the success of carrier fixation in one or more habitats is determined by: the number of carriers released, sizes of habitats, distances between habitats, and the rate of migration between habitats. Besides yielding sensible and potentially useful predictions regarding the success of Wolbachia-based control, our framework applies to other approaches (e.g., gene drives) and contexts beyond the realm of insect pest control.
Aedes aegypti Controls Ae. aegypti: SIT and IIT—An Overview
29003Robert L. Aldridge; Seth Gibson; Kenneth J. Linthicum, Journal of the American Mosquito Control Association, 20:32-49. 2024-03-11 12:34:19.
The sterile insect technique (SIT) and the incompatible insect technique (IIT) are emerging and potentially revolutionary tools for controlling Aedes aegypti (L.), a prominent worldwide mosquito vector threat to humans that is notoriously difficult to reduce or eliminate in intervention areas using traditional integrated vector management (IVM) approaches. Here we provide an overview of the discovery, development, and application of SIT and IIT to Ae. aegypti control, and innovations and advances in technology, including transgenics, that could elevate these techniques to a worldwide sustainable solution to Ae. aegypti when combined with other IVM practices.
DENV-1 Titer Impacts Viral Blocking in wMel Aedes aegypti with Brazilian Genetic Background
28991Corrêa-Antônio, Jessica, Mariana R. David, Dinair Couto-Lima, Gabriela Azambuja Garcia, Milan S. G. Keirsebelik, Rafael Maciel-de-Freitas, and Márcio Galvão Pavan., Viruses, 16. 2024-03-11 10:08:24.
Several countries have been using Wolbachia deployments to replace highly competent native Aedes aegypti populations with Wolbachia-carrying mosquitoes with lower susceptibility to arboviruses such as dengue, Zika, and chikungunya. In Rio de Janeiro, Wolbachia deployments started in 2015 and still present a moderate introgression with a modest reduction in dengue cases in humans (38%). Here, we evaluated the vector competence of wild-type and wMel-infected Ae. aegypti with a Brazilian genetic background to investigate whether virus leakage could contribute to the observed outcomes in Brazil. We collected the specimens in three areas of Rio de Janeiro with distinct frequencies of mosquitoes with wMel strain and two areas with wild Ae. aegypti. The mosquitoes were orally exposed to two titers of DENV-1 and the saliva of DENV-1-infected Ae. aegypti was microinjected into wMel-free mosquitoes to check their infectivity. When infected with the high DENV-1 titer, the presence of wMel did not avoid viral infection in mosquitoes’ bodies and saliva but DENV-1-infected wMel mosquitoes produced lower viral loads than wMel-free mosquitoes. On the other hand, wMel mosquitoes infected with the low DENV-1 titer were less susceptible to virus infection than wMel-free mosquitoes, although once infected, wMel and wMel-free mosquitoes exhibited similar viral loads in the body and the saliva. Our results showed viral leakage in 60% of the saliva of wMel mosquitoes with Brazilian background; thus, sustained surveillance is imperative to monitor the presence of other circulating DENV-1 strains capable of overcoming the Wolbachia blocking phenotype, enabling timely implementation of action plans.
PSRs: Selfish chromosomes that manipulate reproductive development
28974Xinmi Zhang, Patrick M. Ferree, Seminars in Cell and Developmental Biology, 159-160:66-73. 2024-03-05 14:28:18.
B chromosomes are intriguing “selfish” genetic elements, many of which exhibit higher-than-Mendelian transmission. This perspective highlights a group of B chromosomes known as Paternal Sex Ratio chromosomes (PSRs), which are found in several insects with haplo-diploid reproduction. PSRs harshly alter the organism’s reproduction to facilitate their own inheritance. A manifestation of this effect is the conversion of female destined individuals into males. Key to this conversion is the mysterious ability of PSRs to cause elimination of the sperm-inherited half of the genome during zygote formation. Here we discuss how PSRs were discovered, what is known about how they alter paternal chromatin dynamics to cause sex conversion, and how PSR-induced genome elimination is different from other forms of programmed genome elimination in different insects. PSRs also stand out because their DNA sequence compositions differ in remarkable ways from their insect’s essential chromosomes, a characteristic suggestive of interspecies origins. Broadly, we also highlight poorly understood aspects of PSR dynamics that need to be investigated.
Un1Cas12f1 and Cas9 gene drive in HSV1: viruses that ‘infect’ viruses
28972Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianying Zeng, Guanxiong Lei, Tongwen Zhang, Hongsheng Dai, bioRxiv, 2024-03-05 14:11:19.
Synthetic CRISPR-Cas9 gene drive has been developed as a potential tool to control harmful species. However, Cas9 gene drive faces high resistance rate and mitigation strategies developed so far are difficult to implement. Furthermore, studying the resistance to gene drive is time consuming and challenging in higher organisms. We here tackled these two challenges simultaneously by generating Cas9 and Un1Cas12f1 gene drive in a fast-replicating DNA virus, HSV1. We assessed the transmission dynamics and resistance formation through phenotypical staining and next-generation sequencing, and demonstrated that HSV1 supported fast and effective transmission of gene drives, and the Un1Cas12f1 gene drives yielded greater conversion and lower resistance than did the Cas9 gene drives. This positions the Un1Cas12f1 gene drive as a promising alternative, and HSV1 emerges as a dependable and swift platform for gene drive assessment. The gene drive viruses function like pathogens that specifically infect viruses, offering potential applications in attenuating viral infections.
CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males
28970Smidler, A.L., Marrogi, E., Kauffman, J. et al., Scientific Reports, 14. 2024-03-05 13:54:40.
Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
Genome editing in pests: basic science to applications
28908Chen, X., Palli, S.R., Journal of Pest Science, 2024-02-20 15:39:21.
Recent developments in sequencing technologies produced enormous data on gene sequences and the identity of genes in many pest insects and disease vectors. However, the function of many of these genes is unknown. Functional genomics studies to uncover gene function in pest insects are urgently needed. RNA interference methods could be used in some insects but not most due to their variable efficiency among insect pests. Recently developed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system of genome editing method is being developed for use in many insect pests. This technology has already been demonstrated to function in more than 40 insect pest species from seven orders and has contributed to advances in pest biology and the development of improved pest management methods. This review summarizes recent results of CRISPR/Cas9 technology developments and their contributions to advancing the basic and applied science of insect pests and disease vectors.
Deep orange gene editing triggers temperature-sensitive lethal phenotypes in Ceratitis capitata
28906Sollazzo, G., Nikolouli, K., Gouvi, G. et al., BMC Biotechnology, 24. 2024-02-20 15:24:38.
The Mediterranean fruit fly, Ceratitis capitata, is a significant agricultural pest managed through area-wide integrated pest management (AW-IPM) including a sterile insect technique (SIT) component. Male-only releases increase the efficiency and cost-effectiveness of SIT programs, which can be achieved through the development of genetic sexing strains (GSS). The most successful GSS developed to date is the C. capitata VIENNA 8 GSS, constructed using classical genetic approaches and an irradiation-induced translocation with two selectable markers: the white pupae (wp) and temperature-sensitive lethal (tsl) genes. However, currently used methods for selecting suitable markers and inducing translocations are stochastic and non-specific, resulting in a laborious and time-consuming process. Recent efforts have focused on identifying the gene(s) and the causal mutation(s) for suitable phenotypes, such as wp and tsl, which could be used as selectable markers for developing a generic approach for constructing GSS. The wp gene was recently identified, and efforts have been initiated to identify the tsl gene. This study investigates Ceratitis capitata deep orange (Ccdor) as a tsl candidate gene and its potential to induce tsl phenotypes. An integrated approach based on cytogenetics, genomics, bioinformatics, and gene editing was used to characterize the Ccdor. Its location was confirmed on the right arm of chromosome 5 in the putative tsl genomic region. Knock-out of Ccdor using CRISPR/Cas9-NHEJ and targeting the fourth exon resulted in lethality at mid- and late-pupal stage, while the successful application of CRISPR HDR introducing a point mutation on the sixth exon resulted in the establishment of the desired strain and two additional strains (dor 12del and dor 51dup), all of them expressing tsl phenotypes and presenting no (or minimal) fitness cost when reared at 25 °C. One of the strains exhibited complete lethality when embryos were exposed at 36 °C. Gene editing of the deep orange gene in Ceratitis capitata resulted in the establishment of temperature-sensitive lethal mutant strains. The induced mutations did not significantly affect the rearing efficiency of the strains. As deep orange is a highly conserved gene, these data suggest that it can be considered a target for the development of tsl mutations which could potentially be used to develop novel genetic sexing strains in insect pests and disease vectors.
Meiotic drive against chromosome fusions in butterfly hybrids
28892Jesper Boman, Christer Wiklund, Roger Vila, Niclas Backström, bioRxiv, 2024-02-13 21:18:38.
Species frequently differ in karyotype, but heterokaryotypic individuals may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can thus serve as a mechanism for speciation between incipient lineages but their evolution poses a paradox. How does underdominant rearrangements evolve? One solution is the fixation of underdominant chromosomal rearrangements through genetic drift. However, this requires small and isolated populations. Fixation is more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate transmission ratio distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover a transmission bias favoring the fused state at chromosome with unknown polarization in one experiment and a transmission bias favoring the unfused state of derived fusions in both experiments. The latter result support a scenario where chromosome fusions can fix in populations despite counteracting effects of meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that this transmission bias can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why derived fusions may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.
Intra-lineage microevolution of Wolbachia leads to the emergence of new cytoplasmic incompatibility patterns
28889Namias A, Ngaku A, Makoundou P, Unal S, Sicard M, Weill M, PLoS Biology, 2024-02-13 20:25:15.
Mosquitoes of the Culex pipiens complex are worldwide vectors of arbovirus, filarial nematodes, and avian malaria agents. In these hosts, the endosymbiotic bacteria Wolbachia induce cytoplasmic incompatibility (CI), i.e., reduced embryo viability in so-called incompatible crosses. Wolbachia infecting Culex pipiens (wPip) cause CI patterns of unparalleled complexity, associated with the amplification and diversification of cidA and cidB genes, with up to 6 different gene copies described in a single wPip genome. In wPip, CI is thought to function as a toxin-antidote (TA) system where compatibility relies on having the right antidotes (CidA) in the female to bind and neutralize the male’s toxins (CidB). By repeating crosses between Culex isofemale lines over a 17 years period, we documented the emergence of a new compatibility type in real time and linked it to a change in cid genes genotype. We showed that loss of specific cidA gene copies in some wPip genomes results in a loss of compatibility. More precisely, we found that this lost antidote had an original sequence at its binding interface, corresponding to the original sequence at the toxin’s binding interface. We showed that these original cid variants are recombinant, supporting a role for recombination rather than point mutations in rapid CI evolution. These results strongly support the TA model in natura, adding to all previous data acquired with transgenes expression.
Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti
28882McNamara, C.J., Ant, T.H., Harvey-Samuel, T. et al., Nature Communications, 15. 2024-02-13 17:43:47.
The endosymbiotic bacteria Wolbachia can invade insect populations by modifying host reproduction through cytoplasmic incompatibility (CI), an effect that results in embryonic lethality when Wolbachia-carrying males mate with Wolbachia-free females. Here we describe a transgenic system for recreating CI in the major arbovirus vector Aedes aegypti using CI factor (cif) genes from wAlbB, a Wolbachia strain currently being deployed to reduce dengue transmission. CI-like sterility is induced when cifA and cifB are co-expressed in testes; this sterility is rescued by maternal cifA expression, thereby reproducing the pattern of Wolbachia-induced CI. Expression of cifB alone is associated with extensive DNA damage and disrupted spermatogenesis. The strength of rescue by maternal cifA expression is dependent on the comparative levels of cifA/cifB expression in males. These findings are consistent with CifB acting as a toxin and CifA as an antitoxin, with CifA attenuating CifB toxicity in both the male germline and in developing embryos. These findings provide important insights into the interactions between cif genes and their mechanism of activity and provide a foundation for the building of a cif gene-based drive system in Ae. aegypti.
Transforming malaria prevention and control: the prospects and challenges of gene drive technology for mosquito management
28861Yusuf Amuda Tajudeen, Habeebullah Jayeola Oladipo, Iyiola Olatunji Oladunjoye, Muhammad Kamaldeen Oladipo, Hameedat Damilola Shittu, Imam-Fulani Abdulmumeen, Abdullateef Opeyemi Afolabi and Mona Said El-Sherbini, Annals of Medicine, 55. 2024-01-30 17:32:22.
In the era of insecticides and anti-malarial drug resistance, gene drive technology holds considerable promise for malaria control. Gene drive technology deploys genetic modifications into mosquito populations to impede their ability to transmit the malaria parasite. This can be either through the disruption of an essential mosquito gene or the association of gene drive with a desirable effector gene. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene editing tool that precisely modifies mosquito vector DNA sequences and curtails the rate of pathogen transmission. A comprehensive search was conducted in the SCOPUS and MEDLINE databases (via PubMed) until October 2023. The keywords used were related to the principles and mechanisms of gene drive technology, its advantages, and disadvantages, and its ethical and regulatory considerations in sustainable malaria eradication. The development of gene drive enables the preferential inheritance of specific genes in targeted mosquitoes, potentially obstructing the transmission of the Plasmodium parasite. This technology was also studied for the control of other vector-borne diseases such as dengue and chikungunya viruses. Despite its experimental superiority over other traditional methods such as insecticide-treated nets and insecticide sprays, the long-term dynamic interplay of mutation and resistance poses challenges for gene drive efficiency in sustainable malaria control. This commentary elucidates the underlying mechanisms and principles of gene drive technology, underscoring its promise and challenges as a novel strategy to curtail malaria prevalence. Although the release of such genetically modified mosquitoes into the natural environment would result in the eradication of the locally targeted species of mosquitoes, the complete eradication of the entire species remains questionable. Thus, the practical application raises significant ethical and regulatory concerns for further research and risk assessment, including the risk of gene drive spreading to nontarget species in the wider theatre of biodiverse species.
A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations
28857Anderson, M.A.E., Gonzalez, E., Edgington, M.P. et al., Nature Communications, 15. 2024-01-30 16:38:51.
Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.
Evidence of Differences in Cellular Regulation of Wolbachia-Mediated Viral Inhibition between Alphaviruses and Flaviviruses
28852Rainey SM, Lefteri DA, Darby C, Kohl A, Merits A, Sinkins SP., Viruses, 16(1):115. 2024-01-28 13:51:52.
The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses.
Stakeholder engagement in the development of genetically modified mosquitoes for malaria control in West Africa: lessons learned from 10 years of Target Malaria’s work in Mali
28850Bakara Dicko, Souleymane Kodio, Hatouma Samoura, Fatoumata Traoré, Naima Sykes, Mouhamed Drabo, Delphine Thizy, Isabelle Coche, Benjamin Robinson, Kadiatou Sanogo, Bilkissou Yagouré, Samba Diop, Mamadou B. Coulibaly, Frontiers in Bioengineering and Biotechnology, 11. 2024-01-28 13:28:47.
From 2012 to 2023, the Malaria Research and Training Center (MRTC), based out of the University of Sciences, Techniques and Technologies of Bamako (USTTB), was part of the Target Malaria research consortium working towards developing novel gene drive-based tools for controlling populations of malaria vector mosquitoes. As part of this work, Target Malaria Mali has undertaken a range of in-depth engagement activities with the communities where their research is conducted and with other stakeholders nationally. These activities were meant to ensure that the project’s activities took place with the agreement of those communities, and that those communities were able to play a role in shaping the project’s approach to ensure that its eventual outcomes were in line with their needs and concerns. This paper aims to conduct a critical assessment of those 10 years of stakeholder engagement in order to identify good practices which can inform future engagement work on gene drive research in West Africa. It sets out a range of approaches and practices that enabled the Target Malaria Mali team to engage a variety of stakeholders, to share information, collect feedback, and determine community agreement, in a manner that was inclusive, effective, and culturally appropriate. These can be useful tools for those working on gene drive research and other area-wide vector control methods in West African contexts to ensure that their research is aligned with the interests of the communities who are intended to be its ultimate beneficiaries, and to allow those communities to play a meaningful role in the research process.
The haplolethal gene wupA of Drosophila exhibits potential as a target for an X-poisoning gene drive
28845Clancy D. Lawler, Ana Karla Parra Nuñez, Natalia Hernandes, Soumitra Bhide, Isabelle Lohrey, Simon Baxter, Charles Robin, bioRxiv, 2024-01-28 12:54:44.
A synthetic gene drive that targets haplolethal genes on the X-chromosome can skew the sex ratio towards males. Like an ‘X-shredder’ it does not involve ‘homing’ and that has advantages including the reduction of gene drive resistance allele formation. We examine this ‘X-poisoning’ strategy by targeting four of the 11 known X-linked haplolethal/haplosterile genes of Drosophila melanogaster with CRISPR/Cas9. We find that targeting the wupA gene during spermatogenesis skews the sex ratio so fewer than 14% of progeny are daughters. That is unless we cross the mutagenic males to X^XY female flies that bear attached-X chromosomes, which reverses the inheritance of the poisoned X chromosome so that sons inherit it from their father; in which case only 2% of the progeny are sons. These sex ratio biases suggests that most of the CRISPR/Cas9 mutants we induced in the wupA gene are haplolethal but some are recessive lethal. The males generating wupA mutants do not suffer from reduced fertility rather the haplolethal mutants arrest development in the late stages of embryogenesis well after fertilized eggs have been laid. This provides a distinct advantage over genetic manipulation strategies involving sterility which can be countered by the remating of females. We also find that wupA mutants that destroy the nuclear localization signal of shorter isoforms are not haplolethal as long as the open reading frame remains intact. Like D. melanogaster wupA orthologs of D. suzukii and Anopheles mosquitos are found on X chromosomes making wupA a viable X-poisoning target in multiple species.
A bumpy road ahead for genetic biocontainment
28833George, D.R., Danciu, M., Davenport, P.W. et al, Nature Communications, 2024-01-23 18:15:26.
The environmental release of bioengineered organisms is increasingly being suggested for a variety of applications, including bioremediation, biosequestration, bio-mining, environmental biosensing and conservation. The objectives of many environmental release applications shift the goals of biocontainment from preventing organism spread outside of closed spaces (e.g., laboratories or bioreactors) to managing the persistence of engineered organisms and their genetic material in open, dynamic environments. In the scientific literature, discussions of environmental release are often accompanied by calls for robust “intrinsic biocontainment”, where containment mechanisms are genetically engineered into the organism to limit and control its spread and persistence. A number of intrinsic biocontainment approaches have so far been proposed, and can be grouped into two overarching strategies. First, gene-flow barriers attempt to limit the spread of genetic material through lateral gene transfer, which refers to the ability of cells to directly exchange DNA molecules with one another or absorb DNA from external environmental sources. This can be accomplished through conditional lethality strategies (such as toxin anti-toxin systems or targeted DNA degradation), or through limiting plasmid replication or deleting natural competence genes from target cells. Second, strain/host control strategies seek to prevent survival and growth of engineered microbes outside specific environmental conditions using growth restriction and fitness control strategies such as metabolic auxotrophy, kill switches, and conditional essentiality. Over the past decade, researchers and developers have expanded the technical toolkit of intrinsic biocontainment techniques, with new approaches using orthogonal sequences, synthetic auxotrophy, CRISPR-based kill switches, sequence-entanglement, and “cell-free” systems.
The epidemiology of imported and locally-acquired dengue in Australia, 2012–2022
28826Asma Sohail, Katherine L Anders, Sarah L McGuinness, Karin Leder, Journal of Travel Medicine, 2024-01-23 17:13:52.
Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019.
Recombinant venom proteins in insect seminal fluid reduces female lifespan
28821Samuel J. Beach, Maciej Maselko, bioRxiv, 2024-01-23 14:49:23.
The emergence of insecticide resistance has increased the need for alternative pest management tools1,2 Numerous genetic biocontrol approaches, which involve the release of genetically modified organisms to control pest populations, are in various stages of development to provide highly targeted pest control3-7. However, all current mating-based genetic biocontrol technologies function by releasing engineered males which skew sex-ratios or reduce offspring viability in subsequent generations. This allows mated females continue to cause harm (e.g. transmit disease). Here, we demonstrate the first example of intragenerational genetic biocontrol, wherein mating with engineered males reduces female lifespan. The toxic male technique (TMT) involves the heterologous expression of insecticidal proteins within the male reproductive tract that are transferred to females via mating. We demonstrate TMT in Drosophila melanogaster males, which reduce the median lifespan of mated females by 37 - 59% compared to controls mated to wild type males. Agent-based models of Aedes aegypti predict that compared to existing genetic biocontrol technologies, even modest levels of mated female mortality could allow TMT to suppress a female population substantially faster, which is likely to result in reduced disease burdens. TMT presents a novel approach for combatting outbreaks of disease vectors and agricultural pests.
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