Resistance-nodulation-division family bacterial efflux pump (RND efflux pump)

Resistance-nodulation-division (RND) family bacterial efflux pumps are large, tripartite protein complexes primarily found in Gram-negative bacteria that play a critical role in multidrug resistance (MDR) (Nikaido, 2018, Methods in Molecular Biology). These pumps, such as the well-characterized AcrAB-TolC system in Escherichia coli and MexAB-OprM in Pseudomonas aeruginosa, span both the inner and outer membranes to actively expel a wide range of structurally diverse antibiotics, detergents, and dyes directly into the external environment (Li et al., 2015, Drugs). They utilize the proton motive force as an energy source to drive the transport of substrates from the periplasm or cytoplasm (Yamaguchi et al., 2015, Biological and Pharmaceutical Bulletin). Beyond antibiotic resistance, RND pumps are involved in bacterial virulence, quorum sensing, and the maintenance of cellular homeostasis by removing metabolic waste (Piddock, 2006, Nature Reviews Microbiology). Because they are a major cause of clinical treatment failure, RND pumps are significant therapeutic targets for the development of efflux pump inhibitors (EPIs), which aim to restore the efficacy of existing antibiotics by preventing their extrusion (Lomovskaya et al., 2001, Nature Reviews Drug Discovery). Current research focuses on identifying potent, non-toxic inhibitors that can be co-administered with traditional antibiotics to overcome resistance in pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa (Venter et al., 2015, Frontiers in Microbiology).

Other names

RND superfamily transportersMultidrug resistance (MDR) efflux pumpsRND-type efflux systemsAcrAB-TolC systemMexAB-OprM systemTripartite efflux complexes

Efflux pump inhibition (EPI) through competitive or non-competitive binding to the pump's substrate-binding pocket or distal binding site, thereby blocking the extrusion of antibiotics and increasing their intracellular concentration (Lomovskaya et al., 2001, Nature Reviews Drug Discovery).