AcrBspecific

AcrBspecific is a term used in microbiology to describe substrates, inhibitors, or other molecules that interact specifically with the AcrB component of the AcrAB-TolC multidrug efflux pump in Gram-negative bacteria. The phrase is often used to distinguish interactions dominated by the AcrB transporter from those involving AcrA or TolC alone. AcrB-specific recognition influences the efficiency with which compounds are expelled from the cell, contributing to intrinsic and acquired antibiotic resistance.

AcrB is a trimeric inner membrane protein of the resistance-nodulation-division (RND) family. It forms a tripartite assembly with the periplasmic adaptor AcrA and the outer membrane channel TolC to create a continuous conduit that spans the cell envelope. The pump uses the proton motive force to drive conformational changes in each AcrB protomer, enabling substrate binding in proximal and distal pockets, sequential expulsion through TolC, and release into the extracellular space.

AcrB-specific substrates include many clinically relevant antibiotics, dyes, and other toxic compounds. Structural determinants that favor AcrB recognition include hydrophobic, bulky, and aromatic features, though exact preferences vary among substrates. The proximal binding pocket and distal binding pocket within AcrB contribute to substrate specificity and transport efficiency via a functional rotation mechanism.

Understanding AcrB-specific interactions has practical implications for combatting multidrug resistance. Researchers study AcrB inhibitors that aim to block efflux and restore antibiotic activity, as well as strategies to modulate pump expression. The term AcrB-specific is frequently encountered in reviews and experimental reports examining substrate selectivity and inhibitor design for the AcrAB-TolC system.