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Respiratory flexibility in response to inhibition of cytochrome C oxidase in Mycobacterium tuberculosis.
Arora, Kriti; Ochoa-Montaño, Bernardo; Tsang, Patricia S; Blundell, Tom L; Dawes, Stephanie S; Mizrahi, Valerie; Bayliss, Tracy; Mackenzie, Claire J; Cleghorn, Laura A T; Ray, Peter C; Wyatt, Paul G; Uh, Eugene; Lee, Jinwoo; Barry, Clifton E; Boshoff, Helena I.
Affiliation
  • Arora K; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
  • Ochoa-Montaño B; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
  • Tsang PS; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
  • Blundell TL; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
  • Dawes SS; School of Pathology, University of the Witwatersrand, Parktown, Johannesburg, South Africa.
  • Mizrahi V; School of Pathology, University of the Witwatersrand, Parktown, Johannesburg, South Africa MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, South Africa.
  • Bayliss T; Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, United Kingdom.
  • Mackenzie CJ; Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, United Kingdom.
  • Cleghorn LA; Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, United Kingdom.
  • Ray PC; Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, United Kingdom.
  • Wyatt PG; Drug Discovery Unit, College of Life Sciences, James Black Centre, University of Dundee, Dundee, United Kingdom.
  • Uh E; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
  • Lee J; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
  • Barry CE; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
  • Boshoff HI; Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA hboshoff@niaid.nih.gov.
Antimicrob Agents Chemother ; 58(11): 6962-5, 2014 Nov.
Article in En | MEDLINE | ID: mdl-25155596
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberculosis / Electron Transport Complex IV / Drug Resistance, Multiple, Bacterial / Mycobacterium tuberculosis / Antitubercular Agents Language: En Journal: Antimicrob Agents Chemother Year: 2014 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tuberculosis / Electron Transport Complex IV / Drug Resistance, Multiple, Bacterial / Mycobacterium tuberculosis / Antitubercular Agents Language: En Journal: Antimicrob Agents Chemother Year: 2014 Document type: Article Affiliation country: United States