AcrAB-TolC multidrug efflux pump (AcrAB-TolC)

The AcrAB-TolC multidrug efflux pump is a tripartite transport system essential for the intrinsic and acquired drug resistance of Gram-negative bacteria like Escherichia coli [Nikaido & Pagès, 2012; PubMed: 22122760]. It belongs to the Resistance-Nodulation-Division (RND) family and consists of an inner membrane proton-antiporter (AcrB), a periplasmic adapter protein (AcrA), and an outer membrane channel (TolC) [UniProt: P0AE06]. This system actively extrudes a wide array of structurally unrelated compounds, including antibiotics (e.g., fluoroquinolones, tetracyclines), detergents, and bile salts, directly from the periplasm or cytoplasm to the external environment using the proton motive force [Yu et al., 2003; PubMed: 12791993]. In clinical pathology, the upregulation of AcrAB-TolC is a major driver of multidrug resistance (MDR), facilitating the survival of pathogens during intensive antibiotic treatment [Lomovskaya & Bostian, 2006; PubMed: 16408031]. While no AcrAB-specific inhibitors are currently FDA-approved, experimental efflux pump inhibitors (EPIs) such as PAβN and D13-9001 are being studied for their ability to restore the efficacy of traditional antibiotics by blocking substrate binding sites or disrupting the pump's assembly [Vargiu & Nikaido, 2012; PubMed: 23019375].

Other names

AcrAB complexAcrAB-TolC systemAcrB-AcrA-TolC efflux systemRND-type multidrug efflux pump

Efflux pump inhibitors (EPIs) typically act by binding to the hydrophobic distal binding pocket of the AcrB subunit, thereby sterically hindering the binding of antibiotic substrates, or by uncoupling the proton motive force required for the transport cycle [Vargiu & Nikaido, 2012; PubMed: 23019375].