Bacterial multidrug efflux pump (MDR efflux pump)

Bacterial multidrug efflux pumps are specialized membrane proteins that actively expel a broad spectrum of antibiotics, biocides, and metabolic byproducts from the bacterial cell to the external environment (Li et al., 2015, Clinical Microbiology Reviews). These transporters are fundamental drivers of antimicrobial resistance (AMR), as they can lower the intracellular concentration of drugs below therapeutic levels, enabling bacteria to survive and acquire further resistance mutations (Blair et al., 2015, Nature Reviews Microbiology). They are classified into five major families—Resistance-Nodulation-Division (RND), Major Facilitator Superfamily (MFS), ATP-binding cassette (ABC), Small Multidrug Resistance (SMR), and Multidrug and Toxic Compound Extrusion (MATE)—distinguished by their structural organization and energy source (Du et al., 2018, Nature Reviews Microbiology). In clinical settings, the overexpression of these pumps, such as the AcrAB-TolC system in Gram-negative bacteria, is frequently associated with treatment failure in infections caused by pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii (Lomovskaya & Bostian, 2001, Antimicrobial Agents and Chemotherapy). Therapeutic strategies currently focus on developing efflux pump inhibitors (EPIs) that can be co-administered with traditional antibiotics to restore their efficacy and overcome multidrug resistance (Venter et al., 2015, BMC Biology). These inhibitors work by blocking the pump's activity, thereby increasing the accumulation of antibiotics within the cell to lethal levels.

Other names

Bacterial multidrug transporterMultidrug resistance transporterXenobiotic efflux pumpBacterial efflux systemMultidrug efflux pump

Efflux pump inhibitors (EPIs) function through several mechanisms: competitive inhibition by binding to the substrate-binding pocket, non-competitive inhibition by binding to allosteric sites to prevent conformational changes, or by disrupting the energy source of the pump, such as the proton motive force or ATP hydrolysis (Lomovskaya & Bostian, 2001, Antimicrobial Agents and Chemotherapy; Venter et al., 2015, BMC Biology).