Clofazimine exposure in vitro selects efflux pump mutants and bedaquiline resistance [Mechanisms of Resistance]

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 harbouring 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.

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