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Mechanisms of resistance to imipenem in imipenem-resistant, ampicillin-sensitive Enterococcus faecium

N El Amin1, B Lund, A Tjernlund

  • 1Division of Clinical Bacteriology, Huddinge University Hospital, Stockholm, Sweden.

APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica
|March 20, 2002
PubMed

Insights

Imipenem resistance in Enterococcus faecium is linked to overproduction of PBP5, a key protein targeted by beta-lactam antibiotics. This resistance involves decreased PBP5 affinity for imipenem, distinct from ampicillin resistance mechanisms.

Area of Science:

  • Microbiology
  • Antibiotic Resistance
  • Molecular Biology

Background:

  • Enterococcus faecium possesses six penicillin-binding proteins (PBPs), with PBP5 being a primary target for beta-lactam antibiotics.
  • Understanding the mechanisms of antibiotic resistance in E. faecium is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the penicillin-binding protein (PBP) profiles of imipenem-resistant, ampicillin-sensitive E. faecium strains.
  • To elucidate the molecular basis of imipenem resistance in E. faecium, differentiating it from ampicillin resistance.

Main Methods:

  • Analysis of PBP profiles using biotinylated ampicillin and chemiluminescence detection.
  • Sequencing of the pbp5fm gene's penicillin-binding domain in resistant and susceptible strains.
  • Comparison of PBP5 expression levels and imipenem affinity.

Main Results:

  • Imipenem-resistant strains showed hyperproduction of PBP5 compared to susceptible strains.
  • PBP5 from imipenem-resistant strains exhibited decreased affinity for imipenem.
  • Four amino acid substitutions were identified in the PBP5 penicillin-binding domain of resistant strains, though their direct contribution to resistance is unclear.

Conclusions:

  • Moderate imipenem resistance in E. faecium is associated with increased PBP5 production and reduced imipenem affinity.
  • The evolution of imipenem resistance in E. faecium appears distinct from resistance mechanisms observed for other beta-lactams like ampicillin.

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