Resistance-Nodulation-Division efflux pump (RND efflux pump)

Pseudomonas aeruginosa efflux pumps, particularly those belonging to the Resistance-Nodulation-Division (RND) family, are complex tripartite molecular machines that span the inner membrane, periplasm, and outer membrane of the bacterium (Li et al., 2015, Microbiol Mol Biol Rev). These systems, most notably MexAB-OprM and MexXY-OprM, utilize the proton motive force to actively extrude a broad spectrum of antibiotics, including beta-lactams, fluoroquinolones, and aminoglycosides, before they can reach their intracellular targets (Nikaido & Pagès, 2012, Drug Resist Updat). Beyond their role in multidrug resistance, these pumps are essential for the secretion of virulence factors and quorum-sensing molecules, which are critical for biofilm formation and host colonization (Poole, 2005, J Antimicrob Chemother). In clinical settings, the overexpression of these pumps is a primary driver of treatment failure in chronic infections such as those found in cystic fibrosis patients (Lomovskaya et al., 2001, Antimicrob Agents Chemother). Current therapeutic research focuses on the development of efflux pump inhibitors (EPIs) that can be co-administered with traditional antibiotics to potentiate their activity and overcome resistance (Venter et al., 2015, FEBS Lett). However, the structural diversity of the pumps and the potential for host toxicity remain significant hurdles in the clinical translation of these inhibitors.

Other names

Mex-Opr efflux systemMultidrug efflux pumpXenobiotic transporterH+-coupled multidrug efflux pumpTripartite efflux complex

Efflux pump inhibition; competitive or non-competitive binding to the pump's substrate binding pocket or assembly interface to prevent the extrusion of antibiotics and restore bacterial susceptibility.