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Transcriptional Inhibition of the F1F0-Type ATP Synthase Has Bactericidal Consequences on the Viability of Mycobacteria.


ABSTRACT: Bedaquiline, an inhibitor of the mycobacterial ATP synthase, has revolutionized the treatment of Mycobacterium tuberculosis infection. Although a potent inhibitor, it is characterized by poorly understood delayed time-dependent bactericidal activity. Here, we demonstrate that in contrast to bedaquiline, the transcriptional inhibition of the ATP synthase in M. tuberculosis and Mycobacterium smegmatis has rapid bactericidal activity. These results validate the mycobacterial ATP synthase as a drug target with the potential for rapid bactericidal activity.

SUBMITTER: McNeil MB 

PROVIDER: S-EPMC7526845 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Transcriptional Inhibition of the F<sub>1</sub>F<sub>0</sub>-Type ATP Synthase Has Bactericidal Consequences on the Viability of Mycobacteria.

McNeil Matthew B MB   Ryburn Heath W K HWK   Harold Liam K LK   Tirados Justin F JF   Cook Gregory M GM  

Antimicrobial agents and chemotherapy 20200722 8


Bedaquiline, an inhibitor of the mycobacterial ATP synthase, has revolutionized the treatment of <i>Mycobacterium tuberculosis</i> infection. Although a potent inhibitor, it is characterized by poorly understood delayed time-dependent bactericidal activity. Here, we demonstrate that in contrast to bedaquiline, the transcriptional inhibition of the ATP synthase in <i>M. tuberculosis</i> and <i>Mycobacterium smegmatis</i> has rapid bactericidal activity. These results validate the mycobacterial AT  ...[more]

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