Multidrug efflux pump subunit AcrB (AcrB) (AcrB)

AcrB is the essential inner membrane component of the AcrAB-TolC tripartite multidrug efflux system, primarily found in Gram-negative bacteria such as Escherichia coli [1, 2]. It functions as a proton-motive force-driven antiporter that recognizes and extrudes a remarkably broad range of structurally diverse substrates, including various classes of antibiotics, detergents, and dyes [7, 14]. The protein operates as a homotrimer, utilizing a functional rotation mechanism where each protomer cycles through three distinct conformational states—access (loose), binding (tight), and extrusion (open)—to transport molecules from the periplasm to the external environment [8, 11]. AcrB is a major contributor to the multidrug resistance (MDR) phenotype in clinical pathogens, as its overexpression or specific mutations can lead to treatment failure by reducing intracellular drug concentrations [6, 15]. Consequently, AcrB is a high-priority therapeutic target for the development of efflux pump inhibitors (EPIs), which aim to restore antibiotic sensitivity by blocking the pump's activity [1, 17]. These inhibitors typically work by binding to the substrate pockets or allosteric sites, thereby preventing the conformational changes necessary for efflux [3, 9].

Other names

AcrAB-TolC multidrug efflux pump subunit AcrBAcridine resistance protein BAcrB transporterRND-type multidrug efflux pump subunit AcrB

Efflux pump inhibitors (EPIs) target AcrB by binding to its distal or proximal substrate-binding pockets, or to allosteric sites in the transmembrane domain, which prevents the functional rotation of the trimer and blocks the extrusion of antibiotics [1, 3, 9].