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Enterococcal resistance to vancomycin and related cyclic glycopeptide antibiotics
1Infectious Diseases Section, Veterans Administration Medical Center, Cleveland, Ohio.
Abstract:
Enterococci belonging to various species resistant to vancomycin and related cyclic glycopeptide antibiotics have been isolated from hospitalized patients in France, the UK and the USA. All such strains examined display inducible synthesis of a membrane protein associated with resistance. The mechanism by which the membrane protein acts has not been definitively established, but it may block the access of the antibiotic to its peptidoglycan target. That the protein could be a bypass enzyme has not been ruled out. Transfer of glycopeptide resistance by conjugation to either Enterococcus faecium or Enterococcus faecalis and by transformation of Streptococcus sanguis Challis has been reported. The structural and regulatory genes encoding this resistance can be localized on plasmid and, apparently, chromosomal DNA. The plasmids encoding this resistance appear to differ from each other and have variable host ranges, but share at least some DNA sequence homology.
Insights
Vancomycin-resistant enterococci (VRE) strains exhibit inducible membrane protein synthesis linked to resistance. This protein may impede antibiotic access to its target, with resistance genes found on plasmids and chromosomal DNA.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Vancomycin-resistant enterococci (VRE) pose a significant threat in healthcare settings.
- Isolation of VRE from hospitalized patients in France, UK, and USA highlights global concern.
Purpose of the Study:
- To investigate the characteristics of vancomycin resistance in enterococci.
- To elucidate the mechanism of resistance and the genetic basis of its transfer.
Main Methods:
- Isolation and characterization of VRE strains.
- Analysis of membrane protein synthesis and function.
- Investigation of gene transfer mechanisms (conjugation and transformation).
Main Results:
- All VRE strains examined showed inducible synthesis of a membrane protein associated with resistance.
- The mechanism may involve blocking antibiotic access to peptidoglycan targets or acting as a bypass enzyme.
- Glycopeptide resistance genes were found on both plasmid and chromosomal DNA.
- Resistance transfer was demonstrated via conjugation and transformation.
Conclusions:
- A novel membrane protein is implicated in vancomycin resistance in enterococci.
- The genetic determinants of resistance are transferable and can be located on mobile genetic elements.
- Understanding these mechanisms is crucial for combating VRE infections.