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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.

References associated with 2.B.42 family:

Hards, K., D.G.G. McMillan, L.A. Schurig-Briccio, R.B. Gennis, H. Lill, D. Bald, and G.M. Cook. (2018). Ionophoric effects of the antitubercular drug bedaquiline. Proc. Natl. Acad. Sci. USA 115: 7326-7331. 29941569