Abstract

Wolbachia are obligate, intracellular, bacterial endosymbionts present in over 60% of all insect species. Manipulation of host reproduction and efficient maternal transmission have facilitated the global spread of Wolbachia in arthropods. Wolbachia are also present in filarial nematodes and are the leading cause of River Blindness and Elephantiasis. Our lab has focussed on the molecular and cellular interactions that mediate Wolbachia replication and transmission through insect and nematode germlines. Our studies demonstrate that efficient germline transmission of Wolbachia requires a developmentally coordinated association with plus and minus end motor proteins followed by a stable association in conserved germline determinants. In addition, Wolbachia manipulates host chromatin remodelers and the cell cycle to its advantage. Surveys of wild Drosophila populations reveals Wolbachia also stably populates host somatic lineages including the adult brain. Consequently we were able to generate stably Wolbachia infected Drosophila cell lines. This facilitated high-throughput cell-based screens for small molecule compounds that specifically target Wolbachia. We describe the identification of Albendazole sulfone, an FDA approved metabolite of Albendazole, that specifically disrupts Wolbachia replication in Brugia malayi, the nematode associated with Elephantiasis and River Blindness.