Permeability to carbapenems of Proteus mirabilis mutants selected for resistance to imipenem or other beta-lactams

J Antimicrob Chemother. 1997 Sep;40(3):365-70. doi: 10.1093/jac/40.3.365.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amdinocillin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / metabolism
  • Carbapenems / pharmacology*
  • Cefoxitin / pharmacology
  • Cell Membrane Permeability / drug effects
  • Imipenem / pharmacology*
  • Mutation
  • Proteus mirabilis / drug effects
  • Proteus mirabilis / enzymology
  • Proteus mirabilis / metabolism*
  • beta-Lactam Resistance
  • beta-Lactamases / deficiency

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Carbapenems
  • Cefoxitin
  • Imipenem
  • beta-Lactamases
  • beta-lactamase TEM-1
  • Amdinocillin