Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins

J Antimicrob Chemother. 1995 Aug;36(2):335-42. doi: 10.1093/jac/36.2.335.

Abstract

Two strains of Proteus mirabilis, IpR1 and IpR2, resistant to both imipenem and mecillinam, but susceptible to other beta-lactams were isolated from blood cultures of patients who had been treated with imipenem. Strain IpR1 was isolated in the same sample as a P. mirabilis IpS1 which was susceptible to imipenem and mecillinam. Strains IpR1 and IpR2 did not produce a beta-lactamase and their outer membrane protein profiles were similar to those of IpS1 and P. mirabilis ATCC 29906. Electrophoretic profiles of penicillin-binding proteins (PBPs) showed a decrease in PBP 1A of strains IpR1 and IpR2 compared with IpS1 and ATCC 29906. Competition experiments revealed a decrease in affinity of PBP 2 for imipenem from strain IpR1. These findings suggest that imipenem resistance in P. mirabilis might result from altered PBPs, as reported for Acinetobacter baumanii and Pseudomonas aeruginosa.

MeSH terms

  • Amdinocillin / pharmacology
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Proteins*
  • Carrier Proteins / metabolism*
  • Drug Resistance, Microbial
  • Electrophoresis, Polyacrylamide Gel
  • Hexosyltransferases*
  • Humans
  • Imipenem / pharmacology*
  • Isoelectric Focusing
  • Muramoylpentapeptide Carboxypeptidase / metabolism*
  • Penicillin Resistance
  • Penicillin-Binding Proteins
  • Penicillins / pharmacology
  • Peptidyl Transferases*
  • Proteus Infections / microbiology
  • Proteus mirabilis / drug effects*
  • Proteus mirabilis / enzymology
  • Proteus mirabilis / metabolism
  • Thienamycins / pharmacology*
  • beta-Lactamases / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Carrier Proteins
  • Penicillin-Binding Proteins
  • Penicillins
  • Thienamycins
  • Imipenem
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase
  • beta-Lactamases
  • Amdinocillin