Multidrug efflux pump subunit AcrA (AcrA) (AcrA)

Multidrug efflux pump subunit AcrA (AcrA) is a periplasmic membrane fusion protein that serves as an essential adaptor in the tripartite AcrAB-TolC multidrug efflux pump system, primarily in Gram-negative bacteria such as Escherichia coli [3, 4]. It physically and functionally links the inner membrane transporter AcrB to the outer membrane channel TolC, creating a sealed channel that spans the periplasmic space to export toxic substances [2, 11]. By facilitating the extrusion of a broad spectrum of substrates—including antibiotics like fluoroquinolones and tetracyclines, as well as detergents and bile salts—AcrA plays a central role in both intrinsic and acquired bacterial multidrug resistance (MDR) [5, 13]. Because it is indispensable for pump assembly and operation, AcrA has become a high-priority target for the development of efflux pump inhibitors (EPIs) [1, 12]. These inhibitors bind to allosteric sites on AcrA to prevent the formation or function of the efflux complex, effectively restoring the sensitivity of resistant pathogens to existing antibiotic therapies [6, 10]. Targeted inhibition of AcrA offers a promising clinical strategy for overcoming antibiotic resistance in difficult-to-treat bacterial infections [8, 17].

Other names

Periplasmic adaptor proteinMembrane fusion proteinAcridine resistance protein AAcriflavine resistance protein AAcrAB-TolC multidrug efflux pump subunit AcrAlirmtcA

Efflux pump inhibition by binding to the periplasmic adaptor protein, thereby disrupting the assembly or allosteric gating of the tripartite AcrAB-TolC efflux complex and preventing the extrusion of antimicrobial agents.