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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

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Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa

N Masuda1, S Ohya

  • 1Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.

Antimicrobial Agents and Chemotherapy
|September 1, 1992
PubMed

Insights

Multiple-drug-resistant Pseudomonas aeruginosa mutants overproduced the OprM outer membrane protein, leading to cross-resistance to meropenem, cephems, and quinolones. This suggests OprM overproduction is linked to reduced outer membrane permeability.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for developing multidrug resistance.
  • Outer membrane proteins play a crucial role in bacterial susceptibility to antibiotics.

Purpose of the Study:

  • To investigate the mechanisms underlying multidrug resistance in Pseudomonas aeruginosa.
  • To determine the association between outer membrane protein OprM and antibiotic cross-resistance.

Main Methods:

  • Isolation and characterization of multidrug-resistant mutants of Pseudomonas aeruginosa PAO1.
  • Analysis of outer membrane protein expression, specifically OprM.
  • Transduction experiments to assess cotransferability of resistance phenotypes.

Main Results:

  • Mutants resistant to ofloxacin and cefsulodin exhibited increased resistance to meropenem, cephems, carbenicillin, quinolones, tetracycline, and chloramphenicol.
  • Increased production of the 49,000 molecular weight outer membrane protein (OprM) was observed in resistant mutants.
  • Approximately 5% of clinical isolates showed cross-resistance to meropenem, cephems, and quinolones, correlating with OprM overproduction.
  • The multiple-drug resistance and OprM overproduction phenotypes were cotransferable via transduction.

Conclusions:

  • Overproduction of the OprM outer membrane protein is strongly associated with cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa.
  • This association may involve decreased outer membrane permeability to meropenem.
  • OprM overproduction represents a significant mechanism contributing to multidrug resistance in P. aeruginosa.

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