Cross-resistance between clofazimine and bedaquiline through upregulation of mmpl5 in mycobacterium tuberculosis

Abstract

The antileprosy drug clofazimine is also of interest for the treatment of multidrug-resistant tuberculosis. To unDerstand possible resistance mechanisms, clofazimine-resistant Mycobacterium tuberculosis mutants were isolated in vitro, and, unexpectedly, found to be cross-resistant to bedaquiline. Mutations in the transcriptional regulator Rv0678, with concomitant upregulation of the multisubstrate efflux pump, MmpL5, accounted for this cross-resistance. Mutation in Rv0678 should therefore be consiDered a confounding factor for the treatment of tuberculosis with clofazimine or bedaquiline. Copyright © 2014, American Society for Microbiology.