Helicobacter pylori efflux pump (H. pylori efflux pump)

Helicobacter pylori efflux pumps are specialized transmembrane proteins that facilitate the active transport of various molecules, including antibiotics, out of the bacterial cell (Ge et al., 2018 [1]). These pumps are classified into several families, with the Resistance-Nodality-Division (RND) family, particularly the HefABC system, being the primary driver of multidrug resistance in H. pylori (Liu et al., 2005 [2]). By reducing the intracellular accumulation of key antibiotics such as clarithromycin, metronidazole, and levofloxacin, these pumps contribute significantly to treatment failure and the persistence of chronic infections (Kutting et al., 2005 [3]). Beyond antibiotic resistance, these systems are essential for bacterial fitness, aiding in the extrusion of metabolic toxins and maintaining ion homeostasis (Kutschke and de Jonge, 2005 [4]). Efflux pump inhibitors (EPIs), such as phenylalanine-arginine beta-naphthylamide (PAβN), are being investigated as adjunctive therapies to restore antibiotic susceptibility by blocking these transport mechanisms (Nishino et al., 2003 [5]). However, the clinical application of these inhibitors is currently limited by potential toxicity and the challenge of achieving effective concentrations within the gastric mucosa (Tegos et al., 2002 [6]).

Other names

RND-family efflux pumpsHefABCHefDEFHefGHIMultidrug efflux systemsProton-motive force-dependent pumps

Efflux pump inhibitors (EPIs) function by binding to the substrate-binding sites of the pump, disrupting the energy source (such as the proton motive force), or sterically hindering the movement of the pump components, thereby preventing the extrusion of antibiotics and increasing their intracellular concentration (Ge et al., 2018; Nishino et al., 2003).