Gram-negative bacterial outer membrane protein (OMP) (OMP)

Gram-negative bacterial outer membrane proteins (OMPs) are a diverse class of proteins embedded in the asymmetric outer lipid bilayer of Gram-negative bacteria, typically characterized by a conserved beta-barrel structural motif [Fair & Tor, 2014]. These proteins perform essential physiological roles, including the selective uptake of nutrients through porins, the active efflux of waste and antibiotics, and the maintenance of the structural integrity of the cell envelope [Pages et al., 2008]. Because the outer membrane serves as a formidable permeability barrier against many clinical antibiotics, OMPs are central to both the mechanism of drug entry and the development of antimicrobial resistance. Therapeutic strategies targeting OMPs include the direct disruption of membrane stability by polymyxins or the inhibition of essential biogenesis pathways, such as the Beta-barrel Assembly Machinery (BAM) complex and the Lipopolysaccharide transport (Lpt) system [Imai et al., 2019; Sperandeo et al., 2008]. For instance, the novel antibiotic darobactin targets the essential OMP BamA to effectively kill multidrug-resistant pathogens like Acinetobacter baumannii [Imai et al., 2019]. However, the clinical utility of targeting OMPs is frequently challenged by the bacteria's ability to rapidly downregulate or mutate non-essential porins to evade treatment [Pages et al., 2008].

Other names

Outer membrane proteinsBacterial OMPsGram-negative surface proteinsBeta-barrel outer membrane proteins

Inhibition of the beta-barrel assembly machinery (BAM) complex (e.g., darobactin targeting BamA); Inhibition of lipopolysaccharide transport (e.g., murepavadin targeting LptD); Direct disruption of outer membrane integrity (e.g., polymyxins); Utilization of OMP transporters for active drug uptake (e.g., cefiderocol via siderophore receptors).