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AVI ppat. Wolbachia labeled with Syto-11 are visible as short, bright green rods. Host microtubules are indicated by Jupiter-GFP as thin, filamentous lines. Movie represents 80 images acquired over 400 seconds of acquisition time.
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. Millions of people are infected with filarial nematodes that rely upon endosymbiotic Wolbachia bacteria for their survival.
These Wolbachia ultimately induce an immune response that gives rise to African river blindness or lymphatic filariasis. Thus, targeting Wolbachia will prevent induction of disease symptoms while also eliminating the filarial nematode infection.
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