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Updated: Oct 5, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Induction of vancomycin resistance in Enterococcus faecium by inhibition of transglycosylation
1Department of Medicine, Beth Israel Medical Center, New York, NY 10003.
Abstract:
Vancomycin resistance has recently been recognized among clinical isolates of enterococci. Resistance is inducible, and associated with production of a novel 39 kDa membrane protein. The mechanism by which exposure to vancomycin, which does not penetrate the cell membrane, induces resistance is unknown. In the vancomycin resistant strain Enterococcus faecium 228, resistance was also inducible by moenomycin, suggesting that inhibition of the transglycosylation step in peptidoglycan synthesis may be required for induction of resistance. Cytoplasmic pools of peptidoglycan precursors were increased after exposure to vancomycin or moenomycin, representing a potential means for regulation of induction.
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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