AcrBmediated

AcrB-mediated efflux refers to the action of the AcrB protein, a central component of the AcrAB-TolC tripartite efflux pump in many Gram-negative bacteria. This system transports a broad range of substrates, including many clinically relevant antibiotics, out of the cell, contributing to multidrug resistance by reducing intracellular drug concentrations.

AcrB is a homotrimer located in the inner membrane. Each protomer cycles through conformational states in a peristaltic mechanism (commonly described as access, binding, and extrusion states). Substrates enter the inner-membrane-facing pocket, are captured by the transporter, and are expelled through the TolC channel in the outer membrane with the help of the periplasmic adaptor protein AcrA. The pump uses the proton motive force to drive conformational changes.

AcrB substrates are diverse, including beta-lactams, chloramphenicol, tetracyclines, fluoroquinolones, macrolides, and dyes and detergents. The presence and activity of AcrB can therefore lower intracellular antibiotic levels and compromise treatment. In many bacteria, AcrB expression is regulated by global stress response regulators such as MarA, SoxS, and Rob, and by local repression from AcrR; exposure to antibiotics or solvents can induce expression.

Efforts to counter AcrB-mediated resistance include research into efflux inhibitors that block AcrB function, genetic mutations that alter substrate specificity, and strategies to co-administer inhibitors with antibiotics. Understanding AcrB-mediated efflux is essential for interpreting intrinsic resistance in Enterobacteriaceae and for developing approaches to restore antibiotic efficacy.