The Bedaquiline (BDQ) Family 

Bedaquiline, sold under the brand name Sirturo, is a medication used to treat active tuberculosis. It is specifically used to treat multidrug resistant tuberculosis (MDR-TB) when other treatments cannot be used. It is an inhibitor of the mycobacterial F1Fo-ATP synthase, and apparently bind to the c subunit. BDQ ultimately causes mycobacterial cell death as an uncoupling agent. Hards et al. 2018 demonstrated that BDQ can inhibit ATP synthesis in Escherichia coli by functioning as a H⁺/K⁺ ionophore, causing transmembrane pH and potassium gradients to be equilibrated. Despite the apparent lack of a BDQ-binding site, incorporating the E. coli Fo subunit into liposomes enhanced the ionophoric activity of BDQ. The authors discussed the possibility that localization of BDQ at F1Fo-ATP synthases enables BDQ to create an uncoupled microenvironment, by antiporting H⁺/K⁺ Ionophoric properties may be desirable in high-affinity antimicrobials targeting integral membrane proteins.