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Wolbachia  endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new  Wolbachia -disrupting compounds by conducting high-throughput cell-based chemical screens using a  Wolbachia -infected, fluorescently labeled  Drosophila  cell line. This screen yielded several  Wolbachia -disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular  Wolbachia  titer both in  Drosophila melanogaster  and  Brugia malayi , the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt  Drosophila  microtubule organization, suggesting that this compound reduces titer through direct targeting of  Wolbachia . Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces  Wolbachia  elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their  Wolbachia  endosymbionts.

A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia