Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2014;58(1):574-6. doi: 10.1128/AAC.01462-13. Epub 2013 Oct 14.

Abstract

Drug efflux is an important resistance mechanism in Mycobacterium tuberculosis. We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of bedaquiline and clofazimine to M. tuberculosis by 8- to 16-fold. This exquisite susceptibility was noted among drug-susceptible and drug-resistant clinical isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and clofazimine, and efflux may emerge as a resistance mechanism to these drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Diarylquinolines / pharmacology*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Tuberculosis, Multidrug-Resistant
  • Verapamil / pharmacology*

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline
  • Verapamil