Bacterial efflux pumps and membrane ATPases

Bacterial efflux pumps and membrane ATPases are integral membrane proteins essential for bacterial survival, homeostasis, and defense. Efflux pumps are specialized transporters that actively extrude a wide range of substrates, including antibiotics, heavy metals, and toxins, thereby serving as a major mechanism of multidrug resistance (MDR) (Li et al., 2015). These pumps are categorized into several families, such as the Resistance-Nodulation-Division (RND) and ATP-Binding Cassette (ABC) superfamilies, often utilizing the proton motive force or ATP hydrolysis as an energy source (Du et al., 2018). Membrane ATPases, including F-type and P-type ATPases, are responsible for maintaining electrochemical gradients and synthesizing or hydrolyzing ATP to drive cellular work (Kühlbrandt, 2004). In clinical practice, targeting these proteins—such as with the F-type ATPase inhibitor Bedaquiline—provides a potent strategy against recalcitrant infections like tuberculosis (Andries et al., 2005). However, developing inhibitors for these targets is challenging due to the potential for off-target effects on human mitochondrial ATPases or homologous transporters, necessitating high selectivity to ensure patient safety (Piddock, 2006).

Other names

Multidrug resistance (MDR) pumpsBacterial transportersBacterial ATP synthasesEfflux systemsIon-translocating ATPasesRND family transportersABC transporters

Inhibition of ATP synthase activity, competitive inhibition of efflux transporters, disruption of proton motive force, and potentiation of co-administered antibiotics.