Permeability to carbapenems of Proteus mirabilis mutants selected for resistance to imipenem or other beta-lactams.
An imipenem-resistant mutant of Proteus mirabilis lacked a 26 kDa outer membrane protein (OMP). It has previously been postulated that this protein is a porin, but the present mutant, which was cross-resistant to mecillinam but not to other beta-lactams, proved as permeable to carbapenems as its parent. A mecillinam-selected mutant had similar cross-resistance yet retained the 26 kDa OMP, confirming that this protein was not important to resistance. In contrast, cefoxitin-selected mutants retained the 26 kDa protein but had diminished expression of major 41 and 44 kDa OMPs and showed reduced uptake of carbapenems, although this promoted resistance only when a carbapenemase was also present. We conclude that the imipenem-selected mutant owed its resistance to some factor other than porin loss, probably to a lesion in penicillin-binding protein 2.
Villar
H E
HE
Department of Medical Microbiology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Danel
F
F
Livermore
D M
DM
D000560:Amdinocillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D002440:Cefoxitin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D015378:Imipenem / Q000494:pharmacology*; D009154:Mutation; D011513:Proteus mirabilis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000172:deficiency
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D015780:Carbapenems; D002440:Cefoxitin; D015378:Imipenem; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D000560:Amdinocillin