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Outer membrane protein M (OprM) is a critical component of the multidrug efflux systems in the Gram-negative pathogen Pseudomonas aeruginosa [1, 2]. It serves as the outer membrane factor (OMF) or exit duct for several tripartite Resistance-Nodulation-Division (RND) pumps, most notably MexAB-OprM and MexXY-OprM [2, 4]. These systems are primary contributors to both intrinsic and acquired resistance by actively expelling a wide range of antibiotics, including beta-lactams, fluoroquinolones, and aminoglycosides, from the periplasm to the external environment [1, 3]. Structurally, OprM forms a trimeric gated channel consisting of a membrane-embedded beta-barrel and a large periplasmic alpha-helical barrel that docks with its partner proteins [8, 9]. Beyond its role in antibiotic resistance, OprM is involved in the secretion of virulence factors and metallophores such as pseudopaline, which are essential for bacterial survival and metal acquisition during infection [5]. As a central node in multidrug resistance, OprM is a high-priority target for the development of efflux pump inhibitors (EPIs) designed to restore the efficacy of existing antimicrobial therapies [2, 8].
Inhibition of the tripartite efflux pump by blocking the OprM exit channel to prevent the extrusion of antibiotics and restore bacterial sensitivity to antimicrobial agents [2, 8].
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