Induction of vancomycin resistance in Enterococcus faecium by inhibition of transglycosylation

S Handwerger1, A Kolokathis

  • 1Department of Medicine, Beth Israel Medical Center, New York, NY 10003.

Insights

Vancomycin resistance in enterococci is inducible and linked to a new membrane protein. Inhibition of peptidoglycan synthesis may trigger this resistance, increasing precursor pools.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Vancomycin resistance is emerging in clinical enterococcal isolates.
  • This resistance is inducible and linked to a novel 39 kDa membrane protein.
  • The induction mechanism of vancomycin resistance, especially by an extracellular agent, remains unclear.

Purpose of the Study:

  • To investigate the mechanism of vancomycin resistance induction in Enterococcus faecium.
  • To determine if inhibition of peptidoglycan synthesis is involved in vancomycin resistance induction.

Main Methods:

  • Utilized the vancomycin-resistant strain Enterococcus faecium 228.
  • Exposed bacterial cultures to vancomycin and moenomycin.
  • Measured cytoplasmic pools of peptidoglycan precursors.

Main Results:

  • Vancomycin resistance was inducible by both vancomycin and moenomycin.
  • Moenomycin, an inhibitor of transglycosylation, also induced resistance.
  • Exposure to vancomycin or moenomycin led to increased cytoplasmic peptidoglycan precursor pools.

Conclusions:

  • Inhibition of the transglycosylation step in peptidoglycan synthesis is likely required for vancomycin resistance induction.
  • Increased cytoplasmic peptidoglycan precursor pools may play a regulatory role in resistance induction.
  • These findings offer insights into the molecular mechanisms of vancomycin resistance in enterococci.

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