Literature DB >> 25155596

Respiratory flexibility in response to inhibition of cytochrome C oxidase in Mycobacterium tuberculosis.

Kriti Arora1, Bernardo Ochoa-Montaño2, Patricia S Tsang1, Tom L Blundell2, Stephanie S Dawes3, Valerie Mizrahi4, Tracy Bayliss5, Claire J Mackenzie5, Laura A T Cleghorn5, Peter C Ray5, Paul G Wyatt5, Eugene Uh1, Jinwoo Lee1, Clifton E Barry1, Helena I Boshoff6.   

Abstract

We report here a series of five chemically diverse scaffolds that have in vitro activities on replicating and hypoxic nonreplicating bacilli by targeting the respiratory bc1 complex in Mycobacterium tuberculosis in a strain-dependent manner. Deletion of the cytochrome bd oxidase generated a hypersusceptible mutant in which resistance was acquired by a mutation in qcrB. These results highlight the promiscuity of the bc1 complex and the risk of targeting energy metabolism with new drugs.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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Year:  2014        PMID： 25155596      PMCID： PMC4249445          DOI： 10.1128/AAC.03486-14

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


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