Malaria-carrying *Anopheles* mosquitoes are being turned into testbeds for a bacterial infection that could stop them from spreading the parasite. Current insecticide-based tools are losing their effectiveness, and the spread of a new urban mosquito species in Africa threatens to reverse decades of progress. This project tackles a fundamental gap: why a bacterium called *Wolbachia*—which successfully blocks disease in *Aedes* mosquitoes—has been difficult to establish in *Anopheles*. The team has already created stable infections using two different *Wolbachia* strains, giving them a unique resource to dissect the problem. If successful, the work could lead to a self-sustaining, eco-friendly strategy: releasing *Wolbachia*-infected *Anopheles* that are resistant to the malaria parasite, replacing wild populations without insecticides. The research is largely fundamental science, probing how host genetics, gut microbes, and temperature shape this symbiosis. But understanding these rules—rather than relying on trial-and-error injections—could transform a promising biological control into a deployable tool for malaria-endemic countries.
View original technical description
Progress to reduce malaria has subsided due to ineffectiveness of our current vector control tools which are predominantly insecticide-based. The continued invasion of Anopheles stephensi in Africa is a real concern that could enhance urban malaria transmission. Novel control strategies are urgently required. Wolbachia-based biocontrol of Aedes aegypti has achieved unparallel success but progress have been challenging in Anopheles mosquitoes, likely due to the unique biology of strain-specific endosymbiotic interactions. Promisingly, our collaborative team has made profound advancements over the last 10 years. We created the first Wolbachia stable transinfection in An. stephensi using the wAlbB Wolbachia strain from Ae. albopictus and notably have developed a second artificial infection using the wPip Wolbachia strain from Culex pipiens. Therefore, we now have wAlbB and wPip strains in stable symbiosis in both Ae. aegypti and An. stephensi; an invaluable resource for dissecting the influence of strain and host backgrounds on symbiotic relationships. Our team has also identified native Wolbachia strains in An. moucheti and An. demeilloni and have demonstrated that the microbiome impedes Wolbachia vertical transmission in Anopheles with specific bacteria responsible identified for this antagonism. Excitingly, we have pioneered techniques to alter the mosquito gut microbiota enabling us to create mosquitoes with designer microbiomes and rear in closed systems impervious to infection from external microbes. Taken together, these findings, resources and techniques enables us to address critical questions in symbiotic associations between Wolbachia and Anopheles. Here we will examine how host genetic background alters Wolbachia-mediate phenotypes essential for control by exploiting wAlbB and wPip strains in stable symbiosis in Ae. aegypti and An. stephensi. By changing the genetic background of An. stephensi through introgression of diverse backgrounds, we will examine how host genetics alters fitness costs associated with Wolbachia strains. In the second work package, we will investigate vertical transmission of the gut microbiome in Wolbachia-infected and -uninfected Anopheles and determine specific bacterial interactions as gut microbes could be deployed in synergy with Wolbachia to enhance control. The third work package will examine factors that facilitate establishment of Wolbachia in Anopheles, examining how host or bacterial adaptation to the symbiosis facilitates transinfection. While interspecies transfer of Wolbachia has been done in several species, success has been achieved largely through trial and error injecting thousands of embryos, and little has been done to examine factors that enhance transfer success. These questions can only be addressed for Anopheles species by our team given our unique expertise and resources. Finally, we will explore how temperature alters Wolbachia strains’ ability to invade populations and exploit the plasticity in Wolbachiadensity to select for heat-tolerant Wolbachia strain variants in Anopheles. With the threat of malaria re-emerging, our proposal built on a foundation of over 10 years of research including pioneering microbiome engineering techniques is extremely timely. Transforming a susceptible population of Anopheles mosquitoes into a Plasmodium-resistant population unable to transmit parasites would provide a cost-effective and eco-friendly strategy to reduce the burden of malaria leading to significant benefits in malaria-endemic countries.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know