MexABOprM

MexAB-OprM is a tripartite efflux pump in the bacterium Pseudomonas aeruginosa, belonging to the resistance-nodulation-division (RND) family. It exports a broad spectrum of antibiotics and other toxic compounds from the cytoplasm and periplasm to the external environment, contributing to intrinsic and acquired multidrug resistance.

The complex consists of three components: MexB, the inner membrane RND transporter; MexA, a periplasmic adaptor that bridges MexB to OprM; and OprM, an outer membrane channel. MexB uses the proton motive force to translocate substrates, while MexA forms a continuous conduit with OprM, allowing substrates to pass directly from the cytoplasm or periplasm across the outer membrane without entering the external medium.

Expression of MexAB-OprM is tightly regulated. MexR acts as a repressor, and mutations in mexR or alterations in global regulators such as NalC and NalD can derepress transcription, increasing pump abundance and antibiotic resistance. Inducers include various antibiotics and environmental stresses that promote pump expression.

Substrates of MexAB-OprM are diverse and include many beta-lactams (such as some penicillins and cephalosporins), fluoroquinolones, tetracyclines, chloramphenicol, macrolides, and other antimicrobial agents. As a major efflux system, it plays a key role in the intrinsic resistance of P. aeruginosa and can contribute to multidrug resistance in clinical isolates. Inhibition or genetic disruption of the pump is studied as a potential strategy to restore antibiotic susceptibility.

Homologous tripartite efflux systems exist in related bacteria, illustrating a conserved mechanism for multidrug resistance across species.