Respiratory Flexibility in Response to Inhibition of Cytochrome c Oxidase in Mycobacterium tuberculosis | Zendy

Kriti Arora | Zendy; Bernardo OchoaMontaño | Zendy; Patricia Tsang | Zendy; Tom L. Blundell | Zendy; Stephanie S. Dawes | Zendy; Valerie Mizrahi | Zendy; Tracy Bayliss | Zendy; Claire J. Mackenzie | Zendy; Laura A. T. Cleghorn | Zendy; Peter C. Ray | Zendy; Paul G. Wyatt | Zendy; Eugene Uh | Zendy; Jinwoo Lee | Zendy; Clifton E. Barry | Zendy; Helena I. Boshoff | Zendy

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Respiratory Flexibility in Response to Inhibition of Cytochrome c Oxidase in Mycobacterium tuberculosis

Author(s) -

Kriti Arora,

Bernardo OchoaMontaño,

Patricia Tsang,

Tom L. Blundell,

Stephanie S. Dawes,

Valerie Mizrahi,

Tracy Bayliss,

Claire J. Mackenzie,

Laura A. T. Cleghorn,

Peter C. Ray,

Paul G. Wyatt,

Eugene Uh,

Jinwoo Lee,

Clifton E. Barry,

Helena I. Boshoff

Publication year - 2014

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.03486-14

Subject(s) - mycobacterium tuberculosis , microbiology and biotechnology , tuberculosis , cytochrome c oxidase , respiratory system , medicine , biology , immunology , enzyme , biochemistry , pathology

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.

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