Transcriptional Inhibition of the F <sub>1</sub> F <sub>0</sub> -Type ATP Synthase Has Bactericidal Consequences on the Viability of Mycobacteria
Matthew B. McNeil, Heath W. K. Ryburn, Liam K. Harold, Justin F. Tirados, Gregory M. Cook
Abstract
Bedaquiline, an inhibitor of the mycobacterial ATP synthase, has revolutionized the treatment of Mycobacterium tuberculosis infection. Although a potent inhibitor, it is characterized by poorly understood delayed time-dependent bactericidal activity. Here, we demonstrate that in contrast to bedaquiline, the transcriptional inhibition of the ATP synthase in M. tuberculosis and Mycobacterium smegmatis has rapid bactericidal activity. These results validate the mycobacterial ATP synthase as a drug target with the potential for rapid bactericidal activity.
Topics & Concepts
BedaquilineATP synthaseMycobacterium smegmatisMycobacterium tuberculosisMicrobiologyMycobacteriumTuberculosisBiologyChemistryBacteriaEnzymeBiochemistryMedicinePathologyGeneticsATP Synthase and ATPases ResearchTuberculosis Research and EpidemiologyAntibiotic Resistance in Bacteria