Extended-spectrum beta-lactamases and the permeability barrier.
The outer membrane of Gram-negative bacteria represents a barrier for penetration of hydrophilic compounds. Loss of porins (water-filled protein channels) contributes to antimicrobial resistance, particularly when additional mechanisms of resistance are expressed. Many studies on the structure and regulation of porins in Escherichia coli K-12 are available, but there is little information concerning clinical isolates of this species. In Klebsiella pneumoniae, two major porins, OmpK35 and OmpK36, are produced, but many extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates do not express OmpK35. Loss of both OmpK35 and OmpK36 in ESBL-producing K. pneumoniae causes resistance to cefoxitin, increased resistance to expanded-spectrum cephalosporins, and decreased susceptibility to carbapenems, particularly ertapenem. Porin loss also decreases the susceptibility to other non-beta-lactam compounds, such as fluoroquinolones, of ESBL-producing organisms.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000378:metabolism*; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D018272:Porins; D001618:beta-Lactamases