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

The MexAB-OprM efflux pump complex is a major tripartite multidrug resistance system found in the Gram-negative bacterium Pseudomonas aeruginosa (Li et al., 2015). It is composed of three essential proteins: the inner membrane RND-family transporter MexB, the periplasmic membrane fusion protein MexA, and the outer membrane factor OprM (Poole, 2001). This complex functions by utilizing the proton motive force to actively expel a wide range of structurally unrelated antibiotics, including beta-lactams, fluoroquinolones, and macrolides, from the cell before they reach their targets (Nikaido & Pagès, 2012). Its constitutive expression contributes to the intrinsic resistance of P. aeruginosa, while its overexpression—often driven by mutations in regulatory genes like mexR—is a primary cause of acquired multidrug resistance in clinical settings (Lomovskaya & Watkins, 2001). Consequently, MexAB-OprM is a high-priority target for the development of efflux pump inhibitors (EPIs) designed to restore the efficacy of conventional antibiotics against resistant strains (Nakashima et al., 2013). These inhibitors aim to block the pump's activity, thereby increasing the intracellular concentration of antibiotics and lowering the minimum inhibitory concentration (MIC) for the pathogen (Lomovskaya & Watkins, 2001). Despite its clinical importance, no MexAB-OprM inhibitors have yet reached the market, largely due to challenges regarding toxicity and pharmacokinetic properties (Li et al., 2015).

Other names

MexA-MexB-OprMMexAB-OprM multidrug efflux systemMexAB-OprM pump

Efflux pump inhibitors (EPIs) bind to the substrate-binding sites or the hydrophobic pockets of the MexB subunit, thereby sterically hindering the binding and transport of antibiotic substrates or disrupting the assembly of the tripartite complex (Nakashima et al., 2013; Lomovskaya & Watkins, 2001).