MexAB-OprM multidrug efflux pump complex (MexAB-OprM)

The MexAB-OprM multidrug efflux pump complex is a tripartite system in Pseudomonas aeruginosa, consisting of the inner membrane resistance-nodulation-division (RND) transporter MexB, the periplasmic membrane fusion protein MexA, and the outer membrane channel OprM. It spans the inner and outer membranes, using proton motive force to actively export a broad range of substrates from the cytoplasm and periplasm to the extracellular space, including structurally diverse antibiotics (e.g., β-lactams, fluoroquinolones, macrolides), detergents, dyes, organic solvents, quorum sensing molecules, and possibly virulence factors. MexB forms a trimeric pump that recognizes and captures substrates via vestibules and a central cavity, MexA oligomerizes to bridge MexB and OprM, and OprM provides a β-barrel channel open to the exterior. This pump is constitutively expressed at basal levels but upregulated via regulators like CpxR (binding the distal promoter) and mutations in repressors (e.g., MexR, NalD), contributing to intrinsic and acquired multidrug resistance in clinical isolates. Overexpression, particularly in nalB-type strains, reduces intracellular antibiotic accumulation, enabling resistance to multiple drugs and complicating treatment of P. aeruginosa infections such as pneumonia, sepsis, urinary tract infections, and chronic cystic fibrosis cases. Structural studies (e.g., cryo-EM) reveal its assembly and peristaltic mechanism for substrate translocation, informing efflux pump inhibitor development to restore antibiotic efficacy.

Other names

MexAB-OprM efflux pumpMexAB-OprM pump

Efflux pump inhibition (targeting assembly or function to block drug export and restore antibiotic susceptibility)