AcrAB-TolC multidrug efflux pump (AcrAB-TolC) (AcrAB-TolC)

The AcrAB-TolC multidrug efflux pump (AcrAB-TolC) is a tripartite protein complex essential for the survival of Gram-negative bacteria, such as Escherichia coli, in toxic environments (UniProt P31224, P0AE06, P02930). It belongs to the Resistance-Nodulation-Division (RND) family and consists of the inner membrane transporter AcrB, the periplasmic adapter protein AcrA, and the outer membrane channel TolC (Nikaido & Takatsuka, 2009). This machinery functions as a proton-antiporter, using the electrochemical gradient to expel a broad spectrum of antibiotics, detergents, and bile salts directly out of the cell (Yamaguchi et al., 2015). Its ability to recognize and transport diverse chemical structures makes it a major contributor to the multidrug resistance (MDR) phenotype in clinical pathogens (Blair et al., 2015). Targeting this complex with efflux pump inhibitors (EPIs) is a promising strategy to potentiate the activity of existing antibiotics and combat resistant infections (Opperman & Nguyen, 2012). These inhibitors work by binding to the pump's active sites or interfering with the assembly of the tripartite complex, thereby preventing drug extrusion. However, the development of clinical-grade inhibitors remains challenging due to potential toxicity and the complex structural dynamics of the pump (Lomovskaya & Bostian, 2006). Despite these hurdles, AcrAB-TolC remains a high-priority target for overcoming antibiotic resistance in Gram-negative bacteria.

Other names

AcrAB complexAcrAB-TolC systemMultidrug efflux pump AcrAB-TolCRND-type efflux pump

Efflux pump inhibition; competitive or non-competitive binding to the pump subunits (primarily AcrB) to prevent the extrusion of antibiotics, thereby increasing intracellular drug concentration and restoring antibiotic efficacy (Opperman & Nguyen, 2012).