Document Detail


A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.
MedLine Citation:
PMID:  23028321     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Laura R Serbus; Frederic Landmann; Walter M Bray; Pamela M White; Jordan Ruybal; R Scott Lokey; Alain Debec; William Sullivan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-20
Journal Detail:
Title:  PLoS pathogens     Volume:  8     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-05-09     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002922     Citation Subset:  IM    
Affiliation:
Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, USA. lrserbus@ucsc.edu
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MeSH Terms
Descriptor/Qualifier:
Albendazole / analogs & derivatives*,  pharmacology
Animals
Brugia malayi / drug effects,  microbiology*
Cell Line
Drosophila melanogaster / drug effects,  microbiology*
Filariasis / drug therapy*
Microbial Sensitivity Tests
Microtubules / drug effects
Symbiosis
Wolbachia / drug effects*
Grant Support
ID/Acronym/Agency:
F32 GM080192/GM/NIGMS NIH HHS; R25 GM058903/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
1UIC88380G/albendazole sulfone; 54965-21-8/Albendazole
Comments/Corrections

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