title: Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis.
abstract: Drug efflux is an important resistance mechanism in Mycobacterium tuberculosis. We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of bedaquiline and clofazimine to M. tuberculosis by 8- to 16-fold. This exquisite susceptibility was noted among drug-susceptible and drug-resistant clinical isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and clofazimine, and efflux may emerge as a resistance mechanism to these drugs.
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, JHU, Baltimore, Maryland, USA.
authors.forename: Shashank
authors.initials: S
authors.lastname: Gupta
authors.forename: Keira A
authors.initials: KA
authors.lastname: Cohen
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winglee
authors.forename: Mamoudou
authors.initials: M
authors.lastname: Maiga
authors.forename: Bassirou
authors.initials: B
authors.lastname: Diarra
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D064687:Diarylquinolines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D018088:Tuberculosis, Multidrug-Resistant; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline; D014700:Verapamil