| A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia. | |
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MedLine Citation:
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PMID: 23028321 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Laura R Serbus; Frederic Landmann; Walter M Bray; Pamela M White; Jordan Ruybal; R Scott Lokey; Alain Debec; William Sullivan |
Publication Detail:
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Type: Journal Article Date: 2012-09-20 |
Journal Detail:
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Title: PLoS pathogens Volume: 8 ISSN: 1553-7374 ISO Abbreviation: PLoS Pathog. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-10-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101238921 Medline TA: PLoS Pathog Country: United States |
Other Details:
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Languages: eng Pagination: e1002922 Citation Subset: IM |
Affiliation:
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Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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