Outer membrane protein OprM (OprM)

Outer membrane protein OprM is a vital component of the tripartite multidrug efflux systems in the Gram-negative bacterium Pseudomonas aeruginosa, serving as the exit duct for the MexAB-OprM, MexCD-OprJ, and MexXY-OprM complexes (UniProt, 2024; Li et al., 2015). As a member of the Outer Membrane Factor (OMF) family, OprM forms a trimeric channel that spans the outer membrane, allowing the expulsion of diverse substrates, including antibiotics, detergents, and dyes, directly from the periplasm or cytoplasm to the extracellular space (Nakashima et al., 2013). This efflux activity is a primary driver of multidrug resistance (MDR) in P. aeruginosa, rendering many standard-of-care antibiotics, such as carbapenems and fluoroquinolones, ineffective (Lomovskaya et al., 2001). Beyond antibiotic resistance, OprM is implicated in the secretion of quorum-sensing molecules and virulence factors, which are essential for the pathogen's survival and pathogenicity during infection (Minagawa et al., 2012). Consequently, OprM is considered a high-value therapeutic target for efflux pump inhibitors (EPIs) designed to restore antibiotic efficacy (Misra et al., 2015). Current research focuses on small molecules like D13-9001 that can bind to the pump assembly and block the efflux process, though clinical translation remains challenging due to potential toxicity and delivery hurdles (Nakashima et al., 2013; Misra et al., 2015).

Other names

OprMOuter membrane factor OprMMexA-MexB-OprM exit ductTolC-like protein OprMOuter membrane factor (OMF)

Efflux pump inhibition via blocking the exit channel or disrupting the assembly of the tripartite pump complex