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

Antimicrob Agents Chemother. 2020 Jul 22;64(8):e00492-20. doi: 10.1128/AAC.00492-20. Print 2020 Jul 22.


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.

Keywords: ATP synthase; CRISPRi; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate
  • Antitubercular Agents / pharmacology
  • Humans
  • Mycobacterium smegmatis / genetics
  • Mycobacterium tuberculosis* / genetics
  • Tuberculosis*


  • Antitubercular Agents
  • Adenosine Triphosphate