Outer Membrane Porins Contribute to Antimicrobial Resistance in Gram-Negative Bacteria

Abstract

Gram-negative bacteria depend on their cell membranes for survival and environmental adaptation. They contain two membranes, one of which is the outer membrane (OM), which is home to several different outer membrane proteins (Omps). One class of important Omps is porins, which mediate the inflow of nutrients and several antimicrobial drugs. The microorganism’s sensitivity to antibiotics, which are predominantly targeted at internal sites, is greatly influenced by the permeability characteristics of porins. In this review, the properties and interactions of five common porins, OmpA, OmpC, OmpF, OmpW, and OmpX, in connection to porin-mediated permeability are outlined. Meanwhile, this review also highlighted the discovered regulatory characteristics and identified molecular mechanisms in antibiotic penetration through porins. Taken together, uncovering porins’ functional properties will pave the way to investigate effective agents or approaches that use porins as targets to get rid of resistant gram-negative bacteria.

Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors

“…Molecular docking has been widely manipulated for the discovery of novel medications as it is an effective method for rapidly and accurately predicting protein–ligand complex binding energies and biomolecular conformations 29 . Herein, the novel diazepines ligands (3a–3d) and oxazepines ligands (4a–4d) were docked into outer membrane protein A (OMPA) and exo-1,3-beta-glucanase are well-known, appealing therapeutic target proteins for the development of antibacterial and antifungal drugs 30 , 31 . The molecular dock score (Mol dock score) was used to express the binding affinity of the docked molecules as negative binding energy kcal/mol.…”

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection

“…Porin loss is the main source of resistance to various antibiotics, particularly b-lactams [ 59 ]. Porins mediate the inflow of nutrients and several antimicrobial drugs in gram-negative bacteria, and the sensitivity of bacteria to antibiotics is greatly influenced by the porins’ permeability characteristics [ 23 ]. A recent study by Ejaz revealed the effect of porin loss on the development of resistance and suggested the mechanisms for such resistance development.…”

“…However, outer membrane porins are closely associated with antibiotic resistance because they facilitate the passive diffusion of antibiotics through the outer membrane. Moreover, OmpC and OmpF are nonspecific porins involved in antibiotic transport and membrane integrity [ 23 ].…”

Comparative Meropenem Pharmacodynamics and Emergence of Resistance against Carbapenem-Susceptible Non-Carbapenemase-Producing and Carbapenemase-Producing Enterobacterales: A Pharmacodynamic Study in a Hollow-Fiber Infection Model

“…The KPC-carbapenemases are more powerful carbapenem-hydrolyzing enzymes [16] and provided higher meropenem MICs than the OXA-48-carbapenemase. Apparently, the high meropenem MICs of donor K. pneumoniae strains are due to carbapenemase production and alternative heterogeneous resistance mechanisms (i.e., reduced outer membrane permeability [17], efflux pump activation [18]).…”