Ecogenomics of Mosquito-Microbe Symbiosis for Novel Control Strategies of Infectious Diseases

The burden of mosquito-transmitted diseases such as Plasmodium, Dengue, West Nile, Zika, Usutu, or yellow fever continue to increase globally, representing one of the most significant public health threats. In the context of insecticide resistance concomitant to the absence of an efficient vaccine, new strategies that focus on mosquito's microbiota are being developed. In particular the widespread intracellular bacterium Wolbachia, which can limit pathogen transmission and hijack host reproduction, represents one of the most promising tools to control the transmission of disease. Nevertheless, the genomic variability of Wolbachia and its mobilome, together with its influence on pathogen blocking, in interaction with other symbiotic Life in naturally infected vectors, remains largely unknown. In this project, I plan to dissect the mechanisms of interaction between Wolbachia, commensal ("healthy") bacterial communities and pathogens, using cutting-edge 'omics' and molecular approaches. 1.Wolbachia variants: I will use shotgun metagenomes to reconstruct Wolbachia and other symbiotic genomes and investigate the links between Wolbachia genetic variability, density and protection in naturally infected individuals at the organ level. I will explore the extent and potential role of Wolbachia phages in mutualistic traits such as defense through differential expression analyses in native conditions and controlled infection within Culex spp. 2.Midgut microbiota: I will explore the diversity, variability, role, and interaction of midgut symbionts with arboviruses through 16S amplicon sequencing and expression analyses in experimental infections conditions in Culex spp. 3.pWCP: I will investigate the transformation and expression capacity of the first and newly discovered Wolbachia plasmid element. If successful, a Wolbachia transformation technology would represent a new tool for vector control strategies and potentially have a great impact for public health worldwide.