Mycobacterial membrane energetics and transport systems

Mycobacterial membrane energetics and transport systems represent a complex network of proteins and pathways essential for the survival, growth, and pathogenesis of Mycobacterium tuberculosis. This target category includes the oxidative phosphorylation machinery, such as the electron transport chain (ETC) and ATP synthase, which collectively maintain the proton motive force and generate cellular ATP (Cook et al., 2017). It also encompasses vital membrane transporters like MmpL3, which is responsible for the export of trehalose monomycolate required for cell wall assembly (Tahlan et al., 2012). Drugs targeting these systems, such as Bedaquiline (inhibiting ATP synthase) and Telacebec (inhibiting the cytochrome bcc complex), have revolutionized the treatment of multi-drug resistant tuberculosis (Andries et al., 2005; Pethe et al., 2013). These systems are particularly attractive targets because they are required not only during active replication but also for the persistence of dormant mycobacteria in host tissues (Bald & Koul, 2010). However, therapeutic intervention in these pathways often requires careful monitoring for safety concerns like cardiotoxicity and complex drug-drug interactions.

Other names

Mycobacterial respiratory chainMycobacterial oxidative phosphorylation systemMycobacterial membrane-associated energy and transport machineryMtb energetics and efflux systems

Inhibition of ATP synthase, inhibition of the cytochrome bcc-aa3 complex, disruption of the proton motive force, and inhibition of MmpL3-mediated mycolic acid transport.