Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa.
The outer membrane of imipenem-resistant mutants of Pseudomonas aeruginosa was shown to have decreased permeability to imipenem but not to cephaloridine. These experiments were performed with intact cells and liposomes containing imipenem-hydrolyzing beta-lactamase derived from Pseudomonas maltophilia, in both cases utilizing an imipenem concentration of 50 microM. In contrast, liposome swelling assays using imipenem at 8 mM detected no significant difference between the imipenem-resistant mutants and their parents. It was found that the outer membrane of P. aeruginosa has a saturable specific channel through which imipenem travels mainly at low concentrations, whereas at high concentrations this pathway is obscured by diffusion through nonspecific porin channels.
Trias
J
J
Department of Microbiology and Immunology, University of California, Berkeley 94720.
Dufresne
J
J
Levesque
R C
RC
Nikaido
H
H
D002463:Cell Membrane Permeability / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D005786:Gene Expression Regulation; D005798:Genes, Bacterial; D015378:Imipenem / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes; D009154:Mutation; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000302:isolation & purification / Q000378:metabolism
D008081:Liposomes; D015378:Imipenem; D001618:beta-Lactamases