Clofazimine Exposure In Vitro Selects Efflux Pump Mutants and Bedaquiline Resistance

Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02141-18. doi: 10.1128/AAC.02141-18. Print 2019 Mar.

Abstract

Six in vitro clofazimine-resistant spontaneous mutants obtained from a wild-type or pyrazinamide-resistant ATCC reference strain were selected to evaluate bedaquiline cross-resistance. The reverse was conducted for bedaquiline mutants. All clofazimine mutants harboring an rv0678 mutation displayed phenotypic cross-resistance. We observed the same for rv0678 bedaquiline mutants; however, atpE bedaquiline mutants showed no phenotypic cross-resistance. This confirms that upfront clofazimine usage may impact subsequent bedaquiline use due to a shared efflux resistance pathway.

Keywords: bedaquiline; clofazimine; cross-resistance; efflux pump mutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Clofazimine / pharmacology*
  • Diarylquinolines / pharmacology*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Membrane Transport Proteins / genetics*
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / genetics

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • Membrane Transport Proteins
  • bedaquiline
  • Clofazimine