title: 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.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Lausanne, Switzerland.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Hartkoorn
authors.forename: Swapna
authors.initials: S
authors.lastname: Uplekar
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D002991:Clofazimine / Q000494:pharmacology*; D064687:Diarylquinolines / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline; D002991:Clofazimine