Target intelligence / Profile preview

Outer membrane protein M (OprM) (OprM)

Target
OprM
Molecular classification
Outer membrane protein [2, 6], Efflux pump component [2, 8], Outer membrane factor (OMF) [2, 12], Porin-like protein [3, 9]
01

Overview

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].

Other names
Outer membrane factor OprMOprM lipoproteinMexA-MexB-OprM exit ductOuter membrane protein M
02

Mechanism of action

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].

03

Biological functions

Multidrug efflux [1, 2]Antibiotic resistance [2, 3]Metallophore secretion (e.g., pseudopaline) [5]Protein secretion [2, 8]Maintenance of membrane integrity [6]
04

Disease associations

Infection (Pseudomonas aeruginosa) [1, 2]Multidrug resistance (MDR) [2, 4, 8]Nosocomial infection [8]
05

Safety considerations

Rapid emergence of compensatory resistance mechanisms [2]Potential off-target toxicity of efflux pump inhibitors (EPIs) [8]Difficulty in achieving therapeutic concentrations within the bacterial periplasm [2, 13]Broad substrate specificity complicating selective inhibition [2]
06

Interacting drugs

Aztreonam [1]

8 more in the full profile.

07

Biomarkers

oprM mRNA expression levels (detected via RT-PCR) [4]OprM protein expression levels (detected via immunoblotting) [4]Mutations in regulatory genes such as mexR, nalB, nalC, and nalD [4]Antibiotic minimum inhibitory concentration (MIC) shifts [1, 2]

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