Clofazimine Exposure In Vitro Selects Efflux Pump Mutants and Bedaquiline Resistance

Nabila Ismail*, Remco P. H. Peters, Nazir A. Ismail, Shaheed V. Omar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)

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.

Original languageEnglish
Article numberARTN e02141-18
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2019

Keywords

  • bedaquiline
  • clofazimine
  • cross-resistance
  • efflux pump mutants
  • MYCOBACTERIUM-TUBERCULOSIS
  • ATP SYNTHASE

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