Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
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A predatory gene drive for targeted control of self-transmissible plasmids

34734
Ryan Tsoi et al.,  Science Advances,  11. 2025-04-03 17:09:42.
Suppressing plasmid transfer in microbial communities has profound implications due to the role of horizontal gene transfer (HGT) in spreading and maintaining diverse functional traits such as metabolic functions, virulence factors, and antibiotic resistance. However, existing tools for inhibiting HGT are limited in their modes of delivery, efficacy, and scalability. Here, we present a versatile denial-of-spread (DoS) strategy to target and eliminate specific conjugative plasmids. Our strategy exploits retrotransfer, whereby an engineered DoS plasmid is introduced into host cells containing a target plasmid. Acting as a predatory gene drive, DoS propagates itself at the expense of the target plasmid, through competition or active elimination. Once the target plasmid is eradicated, DoS is removed via induced plasmid suicide, resulting in a community containing neither plasmid. The strategy is tunable and scalable for various conjugative plasmids, different mechanisms of plasmid inheritance interruption, and diverse environmental contexts. DoS represents a new tool for precise control of gene persistence in microbial communities.

Global asymptotic stability in a delay stage structured model for mosquito population suppression

34720
Huang, Mg., Yu, Js.,  Applied Mathematics,  40:112-136. 2025-03-31 14:42:25.
A promising avenue to control mosquito-borne diseases such as dengue, malaria, and Zika involves releasing male mosquitoes carrying the bacterium Wolbachia in wild areas to drive female sterility by a mechanism called cytoplasmic incompatibility (CI). In this work, we initiate a preliminary assessment of how the combined impact of dispersal, incomplete CI and mating competitiveness on mosquito population suppression by a delay differential equation model. Our theoretical analyses indicate that the immigration of eggs plays a significant role in the suppression dynamics. For the case without egg immigration, we identify a threshold dispersal rate v* of adult mosquitoes, threshold CI density ξ*, and threshold release ratio r*. A successful mosquito suppression would be established only when v < v*, ξ > ξ*, and r(t) ≥ r* uniformly. The immigration of eggs causes the threshold dynamics to be invalid, and warns an absolute failure of population suppression. The monotonicity of the adult steady-state in the dispersal rate and CI intensity indicates that choosing a suitable Wolbachia strain with strong CI intensity, or bringing down the dispersal rate of mosquitoes by blocking the suppression zones is a feasible strategy to obtain a better suppression level.

Exploiting Wolbachia as a Tool for Mosquito-Borne Disease Control: Pursuing Efficacy, Safety, and Sustainability

34677
Moretti, R., Lim, J. T., Ferreira, A. G. A., et al,  Pathogens,  14:285. 2025-03-28 09:41:16.
Despite the application of control measures, mosquito-borne diseases continue to pose a serious threat to human health. In this context, exploiting Wolbachia, a common symbiotic bacterium in insects, may offer effective solutions to suppress vectors or reduce their competence in transmitting several arboviruses. Many Wolbachia strains can induce conditional egg sterility, known as cytoplasmic incompatibility (CI), when infected males mate with females that do not harbor the same Wolbachia infection. Infected males can be mass-reared and then released to compete with wild males, reducing the likelihood of wild females encountering a fertile mate. Furthermore, certain Wolbachia strains can reduce the competence of mosquitoes to transmit several RNA viruses. Through CI, Wolbachia-infected individuals can spread within the population, leading to an increased frequency of mosquitoes with a reduced ability to transmit pathogens. Using artificial methods, Wolbachia can be horizontally transferred between species, allowing the establishment of various laboratory lines of mosquito vector species that, without any additional treatment, can produce sterilizing males or females with reduced vector competence, which can be used subsequently to replace wild populations. This manuscript reviews the current knowledge in this field, describing the different approaches and evaluating their efficacy, safety, and sustainability. Successes, challenges, and future perspectives are discussed in the context of the current spread of several arboviral diseases, the rise of insecticide resistance in mosquito populations, and the impact of climate change. In this context, we explore the necessity of coordinating efforts among all stakeholders to maximize disease control. We discuss how the involvement of diverse expertise—ranging from new biotechnologies to mechanistic modeling of eco-epidemiological interactions between hosts, vectors, Wolbachia, and pathogens—becomes increasingly crucial. This coordination is especially important in light of the added complexity introduced by Wolbachia and the ongoing challenges posed by global change.

Adjacent spillover efficacy of Wolbachia for control of dengue: emulation of a cluster randomised target trial

34679
Lim, J.T., Mailepessov, D., Chong, C.S. et al.,  BMC Medicine,  23. 2025-03-28 08:29:31.
Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wild-type females yield non-viable eggs, thereby suppressing Ae. aegypti abundance in the field. We evaluated the spillover efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue in sites adjacent to release sites (spillover sites). The protocol of a two-arm cluster-randomised test-negative controlled trial (cRCT) was specified and emulated using a nationally representative dengue test-negative/positive database of 454,437 individuals reporting for febrile illness to primary or secondary care in public healthcare institutions. Spillover intervention sites were defined by geolocating locations which were adjacent to, i.e. shared geographical borders with, actual Wolbachia intervention sites. We built a cohort of individuals who resided in spillover sites versus a comparator control group who resided in sites which did not receive Wolbachia interventions. We emulated a constrained randomisation protocol used in cRCTs to balance dengue risk between spillover and control arms in the pre-intervention period. We matched individuals reporting for testing in intervention and control groups by calendar time and a high-dimensional battery of sociodemographic, environmental and anthropogenic variables. Intention-to-treat analysis was conducted to estimate the protective efficacy against dengue given spillover Wolbachia exposure. The final cohort consisted of 2354 matched individuals residing in Wolbachia spillover and control sites for at least 3 months in the study period. Compared to the controls, individuals residing in spillover sites for 3 or more months were associated with a 45% (OR: 0.55, 95% CI: 0.42‒0.74) reduction in risk of contracting dengue. Higher durations of spillover Wolbachia exposure also modestly increased protective efficacies. Compared to the control arm, the proportion of virologically confirmed dengue cases was lower in the spillover arm overall and across each subgroup. Protective efficacies were found across all years, age and sex subgroups. Our results demonstrated the potential of Wolbachia-mediated sterility for reducing the risk of contracting dengue even in sites which were not directly treated by the intervention.

Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi

34659
Larrosa-Godall, M., Ang, J.X.D., Leftwich, P.T. et al.,  Parasites & Vectors,  18. 2025-03-25 09:18:22.
Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk of urban transmission. Urgent efforts are required to develop novel and more efficient strategies for targeted vector control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene drives have the potential to spread a desired trait through a population at higher rates than via normal Mendelian inheritance, even in the presence of a fitness cost. Several target genes have been suggested and tested in different mosquito vector species such as Anopheles gambiae and Aedes aegypti. Several promising suppression drives have been developed in An. gambiae that target the sex determination gene doublesex (dsx). In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). Here, a transgenic line which expresses Cas9 under the control of the endogenous zpg promoter was generated. Separately a transgenic line which expresses a gRNA targeting the female specific exon of dsx was inserted into that same target site. The reproductive fitness of males and females heterozygous and homozygous for this element was determined. A series of experimental crosses was performed to combine the two elements and assess the homing rate of the dsx element in a split drive system. The drive was able to home in a super-Mendelian rate comparable to those obtained by an autonomous drive in this species. Although inheritance rates as high as 99.8% were observed, potentially providing very potent gene drive, dominant effects on male and female fertility were observed, which would be sufficient to hinder spread of such a drive. Molecular analysis indicated that the gRNA expressing insertion disrupted normal splicing of dsx. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in Anopheles stephensi. Although high homing rates were observed, the fitness defects found in both males and females carrying the transgene would likely prohibit this drive from functioning in the field.

Functional constraints of wtf killer meiotic drivers

34646
Nidamangala Srinivasa A., Campbell S., Venkatesan S., et al.,  PLOS Genetics,  21. 2025-03-21 14:59:22.
Diploid organisms, such as humans, have two copies of most genes. Only one copy, however, is transmitted through gametes (e.g., sperm and egg) to any given offspring. Alternate copies of the same gene are expected to be equally represented in the gametes, resulting in random transmission to the next generation. However, some genes can “cheat” to be transmitted to more than half of the gametes, often at a cost to the host organism. Killer meiotic drivers are one such class of cheater genes that act by eliminating gametes lacking the driver. In this work, we studied the wtf family of killer meiotic drivers found in fission yeasts. Each wtf driver encodes a poison and an antidote protein to specifically kill gametes that do not inherit the driver. Through analyzing a large suite of diverse natural and engineered mutant wtf genes, we identified multiple properties—such as poison self-assembly and poison-antidote co-assembly—that can constrain poison toxicity and antidote rescue. These constraints could influence the evolution of wtf genes. Additionally, we discovered several incompatible wtf poison-antidote pairs, demonstrating expanded potential for self-killing wtf alleles. Such alleles could potentially arise spontaneously in populations cause infertility.

Mark-Release-Recapture of Packed and Shipped Aedes aegypti with Wolbachia: Implications for Conducting Remote Incompatible Insect Technique Programs

34640
Ohm, J. R., Lynd, A., McGowan, A., et al.,  The American Journal of Tropical Medicine and Hygiene,  2025-03-21 14:44:30.
Male mosquitoes containing the endosymbiont Wolbachia (Wb+) can be used as a tool to suppress wild mosquito populations through a technique termed incompatible insect technique (IIT). IIT programs reduce wild mosquitoes via incompatible matings between released males and wild females to reduce the number of viable offspring produced in the next generation. Successful programs rely on regular release of incompatible males to outcompete wild males for female mates. Past IIT programs have relied on local production of Wb+ males to support regular releases of incompatible males. Here, we evaluated the survival and dispersal of packed and shipped Wb+ Aedes aegypti males in mark-release-recapture studies at a release site in the British Virgin Islands (BVI), separated by over 3,600 miles from the centralized production facility. Released mosquitoes were recaptured using BG-Sentinel 2 traps collected daily for up to 7 days after release. Wb+ male mosquitoes packed and shipped from a centralized production facility performed similarly to males that were locally reared in the BVI in survival, dispersal, and recapture rates. Our results support the conclusion that packing and shipping live Wb+ male mosquitoes does not impact their ability to survive and disperse in release sites and suggests that IIT mosquito control programs can feasibly be conducted nearly anywhere in the world without the need for local mosquito production facilities.

Gene drives. Technologies for spreading genetic modifications in populations. TAB-Fokus

34652
König, H., Kolleck, A., Sauter, A.,  TAB-Fokus,  48. 2025-03-21 07:04:16.
Gene drives have the potential to help solve major challenges, including the fight against invasive species or vector-borne diseases such as malaria. These hopes are offset by technical and scientific challenges as well as environmental risks. The policy brief TAB-Fokus no. 48 on the opportunities and risks of a technology for spreading desirable traits in populations summarises the most important results of the TA project for the German Bundestag on four pages (and is also available as a web version - see relation in KITopen). Detailed results can be found in the final report - see relation in KITopen).

Engineering drive–selection balance for localized population suppression with neutral dynamics

34597
Willis, K., and Burt, A.,  Proceedings of the National Academy of Sciences,  122. 2025-03-18 10:29:28.
While the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for many species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localized. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here, we describe a way to closely approximate this balance using a toxin–antidote genetic construct that causes recessive lethality or sterility, encodes a genomic editor that makes dominant lethal or sterile edits in the genome, and provides protection against the action or consequences of the editing. Computer modeling shows that this design can be 100-fold more efficient than sterile males, increasing to 1,000-fold when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.

Gene drive: communication, hype, and the publics

34577
Boëte, C.,  Journal of Medical Entomology,  2025-03-12 16:35:04.
Engineered gene drive (EGD) systems are probably the most high-tech approach considered for their potential role in the control of vector-borne diseases. Interestingly, the rhetoric around it often goes along with a negative presentation of the current “conventional” tools and exaggerated promises about EGD themselves, leading to a situation of hype.

wStri spread dynamics in Nilaparvata lugens via discrete mathematical models

34574
Zheng, B., Yang, H., Elaydi, S. et al.,  Journal of Mathematical Biology,  90. 2025-03-12 16:30:16.
Wolbachia, an intracellular bacterium, is well-known for inducing cytoplasmic incompatibility, which has become a promising and environmentally sustainable strategy for controlling pest populations. The strain wStri, specifically identified in Nilaparvata lugens (brown planthopper), has shown potential for such biocontrol applications. In this study, we develop a comprehensive discrete mathematical model to analyze the dynamics of wStri spread in a mixed population of wStri-infected, wLug-infected, and uninfected Nilaparvata lugens under both constant and periodically varying environmental conditions. Under a constant environment, the model identifies the critical threshold necessary for the successful establishment of wStri within the population. Our analysis reveals that the model exhibits a strong Allee effect, where a population must exceed a certain critical density-the Allee threshold-for the wStri strain to persist and spread. Below this threshold, the wStri strain is likely to be eliminated, failing in pest control efforts. When the environment varies periodically, the model transforms into a non-autonomous periodic discrete model, introducing additional complexity. In this scenario, we derive sufficient conditions that ensure the composition of finitely many Allee maps continues to function as an Allee map. Furthermore, we prove that a unique periodic orbit exists within such a periodic environment. This orbit is characterized as unstable and acts as a threshold, determining whether wStri will establish itself in the population or die out over time. The findings from this model provide critical insights into the conditions under which wStri can be effectively used to control Nilaparvata lugens, particularly in environments that are not constant but fluctuate periodically. These insights have significant implications for the practical deployment of Wolbachia-based biocontrol methods in pest management strategies.

A comparative assessment of self-limiting genetic control strategies for population suppression

34572
Yue Han, Jackson Champer,  Molecular Biology and Evolution,  2025-03-12 16:21:17.
Genetic control strategies are promising solutions for control of pest populations and invasive species. Methods utilizing repeated releases of males such as Sterile Insect Technique (SIT), Release of Insects carrying a Dominant Lethal (RIDL), self-limiting gene drives, and gene disruptors are highly controllable methods, ensuring biosafety. Although models of these strategies have been built, detailed comparisons are lacking, particularly for some of the newer strategies. Here, we conducted a thorough comparative assessment of self-limiting genetic control strategies by individual-based simulation models. Specifically, we find that repeated releases greatly enhance suppression power of weak and self-limiting gene drives, enabling population elimination with even low efficiency and high fitness costs. Moreover, dominant female sterility further strengthens self-limiting systems that can either use gene drive or disruptors that target genes without a mechanism to bias their own inheritance. Some of these strategies are highly persistent, resulting in relatively low release ratios even when released males suffer high fitness costs. To quantitively evaluate different strategies independent from ecological impact, we proposed constant-population genetic load, which achieves over 95% accuracy in predicting simulation outcomes for most strategies, though it is not as precise in a few frequency-dependent systems. Our results suggest that many new self-limiting strategies are safe, flexible, and more cost-effective than traditional SIT and RIDL, and thus have great potential for population suppression of insects and other pests.

CRISPR/Cas9 Genome Editing in the Diamondback Moth: Current Progress, Challenges, and Prospects

34556
Asad, M., Chang, Y., Liao, J., & Yang, G.,  International Journal of Molecular Sciences,  26:1515. 2025-03-04 11:34:07.
The development of site-specific genome-editing tools like CRISPR (clustered regularly interspaced short palindromic repeat) and its associated protein, Cas9, is revolutionizing genetic engineering with its highly efficient mechanism, offering the potential for effective pest management. Recently, CRISPR/Cas9 gene-editing has been extensively utilized in the management of the diamondback moth, Plutella xylostella (L.), a highly destructive pest of vegetable crops, for different purposes, such as gene function analysis and genetic control. However, the progress related to this gene-editing tool in P. xylostella has not yet been summarized. This review highlights the progress and applications of CRISPR/Cas9 in uncovering the genes critical for development, reproduction, and insecticide resistance in P. xylostella. Moreover, the progress related to the CRISPR/Cas9 gene drive for population suppression and modifications has also been discussed. In addition to the significant progress made, challenges such as low germline editing efficiency and limited homology-directed repair remain obstacles to its widespread application. To address these limitations, we have discussed the different strategies that are anticipated to improve the efficiency of CRISPR/Cas9, paving the way to it becoming a pivotal tool in sustainable pest management. Therefore, the present review will help researchers in the future enhance the efficiency of the CRISPR/Cas9 system and use it to manage the diamondback moth.

Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae

34552
Andrea L Smidler, Eryney A Marrogi, Sean Scot, et al.,  bioRxiv,  2025-03-04 11:03:46.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange (RMCE) gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired haplolethal-haplosufficient (Ribosome-Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants that reveal a major hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for future development of gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.

Reenacting a mouse genetic evolutionary arms race in yeast reveals that SLXL1/SLX compete with SLY1/2 for binding to Spindlins

34550
M.F. Arlt,A.N. Kruger,C.M. Swanepoel,& J.L. Mueller,  Proceedings of the National Academy of Sciences,  122. 2025-03-04 10:54:14.
In the house mouse, an evolutionary arms race between proteins encoded by the X-linked Slxl1/Slx and Y-linked Sly gene families during spermatogenesis can distort offspring sex ratio, but how these proteins compete remains unknown. We report how SLXL1/SLX competes with SLY1/SLY2 by demonstrating their dose-dependent competitive binding to Spindlins, the key protein domains and rapidly evolving residues and exons that drive the competition, and how the competition is likely between complex multimers. Our findings have broad implications for the mechanics of evolutionary arms and how competition between sex chromosomes influences X- versus Y-sperm fitness and sex ratio.

RNA-guided nucleases enable a gene drive of insertion sequences in plasmids

34547
Kepler S. Mears, Fernando W. Rossine, Natalia Quinones-Olvera, et al.,  bioRxiv,  2025-03-04 10:40:44.
Mobile genetic elements (MGEs) and the interactions between them are a major source of evolutionary innovation. Insertion sequences, the simplest MGEs usually encoding only the necessary genes for transposition and maintenance, are widespread in bacterial genomes, and are particularly common in plasmids. Plasmids, self-replicating extrachromosomal DNA elements, often exist in multiple copies imparting a stochastic barrier to the fixation of an insertion sequence by limiting the proportion of the plasmid population harboring the IS. In this work we demonstrate that to overcome this, the IS200/605 family of insertion sequences utilizes programmable RNA guided nucleases as gene drive to spread the IS through the plasmid population. TnpB, the likely ancestor of Cas12, records the specific insertion site of the IS in its RNA guide to prevent loss of the IS during transposition. When introduced to a plasmid TnpB will be reprogrammed to target and cleave IS-plasmids, resulting in biased replication of IS+ plasmids. Furthermore, the gene drive activity is critical for the IS to invade high copy plasmid populations. Because TnpB can only be mobilized between microbes on other mobile genetic elements, this advantage to fixing in plasmids may help explain the prevalence of TnpB across the tree of life. More generally, the unique pressures arising from movement between genetic contexts with different multiplicities shapes the evolution of strategies for MGE spread.

Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies

34543
Bhattacharyya, 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.

Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease

34533
French, S., Da Silva, R., Storm, J. et al.,  Parasites & Vectors,  18. 2025-02-21 11:33:53.
Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors.

Antagonistic kinesin-14s within a single chromosomal drive haplotype

34531
Meghan J. Brady, Anjali Gupta, Jonathan I. Gent, et al.,  bioRxiv,  2025-02-21 10:31:41.
In maize, there are two meiotic drive systems that operate on large tandem repeat arrays called knobs that are found on chromosome arms. One meiotic drive haplotype, Abnormal chromosome 10 (Ab10), encodes two kinesin proteins that interact with two distinct tandem repeat arrays in a sequence-specific manner to confer meiotic drive. The kinesin KINDR associates with knob180 repeats while the kinesin TRKIN associates with TR-1 repeats. Prior data show that meiotic drive is conferred primarily by the KINDR/knob180 system, with the TRKIN/TR-1 system having little or no role. The second meiotic drive haplotype, K10L2, shows low levels of meiotic drive and only encodes the TRKIN/TR-1 system. Here we used long-read sequencing to assemble the K10L2 haplotype and showed that it has strong homology to an internal portion of the Ab10 haplotype. We also carried out CRISPR mutagenesis of Trkin to test the role of Trkin on Ab10 and K10L2. The data indicate that the Trkin gene on Ab10 does not improve drive or fitness but instead has a weak deleterious effect when paired with a normal chromosome 10. The deleterious effect is more severe when Ab10 is paired with K10L2: in this context functional Trkin on either chromosome nearly abolishes Ab10 drive. We modeled the effect of Trkin on Ab10 and found it should not persist in the population. We conclude that Trkin either confers an advantage to Ab10 in untested circumstances or that it is in the process of being purged from the Ab10 population.

Implications of successive blood feeding on Wolbachia-mediated dengue virus inhibition in Aedes aegypti mosquitoes

34529
Rebecca M. Johnson, Mallery I. Breban, Braiya L. Nolan, et al.,  bioRxiv,  2025-02-21 10:22:32.
Dengue virus (DENV) is a mosquito-borne virus that poses a continued and increasing threat to public health. A promising strategy to mitigate the burden of DENV is introgression of the virus-inhibiting Wolbachia pipientis bacterium into Aedes aegypti populations in the field. While previous studies on Wolbachia-mediated virus inhibition have typically assessed viral replication following a single bloodmeal, the main vector of DENV, Ae. aegypti, feeds frequently, often biting multiple hosts per gonotrophic cycle and promptly attempting to refeed following egg laying. Previously, we demonstrated that successive blood feeding reduces the extrinsic incubation period (EIP) and shortens the time it takes for a mosquito to be able to transmit viruses to a new host. With this in mind, we investigated the impact of successive blood meals on DENV serotype 2 (DENV-2) in Ae. aegypti in the presence or absence of Wolbachia (wAlbB and wMelM). We found that both WT and Wolbachia transinfected had increased DENV-2 dissemination 7 days post-infection as well as higher body titers of DENV-2 in the double-fed groups. Using these empirical data in a binomial regression model, we estimated that successive feeding increased the probability of WT and Wolbachia transinfected mosquitoes surviving the EIP. When we estimated the odds of surviving the EIP for mosquitoes with Wolbachia relative to WT mosquitoes, successive feeding increased the chances of WT mosquitoes surviving the EIP more than in mosquitoes with Wolbachia, indicating a strong inhibitory effect of Wolbachia even in the context of natural frequent blood feeding behavior. Our work shows that mosquito feeding behavior should be considered when assessing the inhibitory effects of Wolbachia on DENV.

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