title: Emergence of resistance to imipenem in Pseudomonas aeruginosa.
abstract: The emergence of resistance to imipenem by Pseudomonas aeruginosa was investigated with four pairs of isolates. Each pair represented pretherapy (susceptible) and posttherapy (resistant) specimens. In all cases, the imipenem-resistant isolates did not demonstrate changed susceptibilities to other beta-lactams. Agarose gel electrophoresis revealed no change in plasmid profiles between any pair of isolates. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the Sarkosyl-insoluble membrane protein revealed the loss of an outer membrane protein of apparent molecular mass 48 to 49 kilodaltons in posttherapy strains when grown with imipenem selection (5 micrograms/ml). There was no significant difference in the binding of [14C]imipenem to the penicillin-binding proteins of the pre- and posttherapy strains. Trichloroacetic acid precipitation of membranes isolated after growth in the presence of [14C]imipenem revealed that significantly less drug was bound to Sarkosyl-soluble membrane protein in three of the four posttherapy strains than the membrane proteins of the respective pretherapy strains. beta-Lactamase activity against imipenem at 100 or 3 microM was not detected in any isolate either with or without induction. These data suggest that resistance to imipenem is associated with the loss of a 48- to 49-kilodalton outer membrane protein accompanied by, in three of four cases, decreased penetration of the antibiotic across the outer membrane.
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D006602:Hexosyltransferases; D015378:Imipenem; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D012967:Sodium Dodecyl Sulfate; D013050:Spectrometry, Fluorescence; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D013845:Thienamycins; D012967:Sodium Dodecyl Sulfate; D015378:Imipenem; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases