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VanD-type vancomycin-resistant Enterococcus faecium and Enterococcus faecalis.

Florence Depardieu1, Mathias Kolbert, Hendrik Pruul

  • 1Unité des Agents Antibactériens, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France. pcourval@pasteur.fr

Antimicrobial Agents and Chemotherapy
|September 25, 2004
PubMed
Summary
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Four Enterococcus strains with constitutive vancomycin resistance were identified. Mutations in ddl, vanS(D), or vanR(D) genes lead to this resistance, offering insights into vancomycin resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Enterococcus species are significant causes of nosocomial infections.
  • Vancomycin resistance in Enterococcus is a growing public health concern.
  • The vanD gene cluster confers resistance to vancomycin through altered peptidoglycan synthesis.

Purpose of the Study:

  • To investigate the genetic basis of constitutive vancomycin resistance in four clinical Enterococcus isolates.
  • To characterize mutations in the ddl, vanS(D), and vanR(D) genes associated with vancomycin resistance.
  • To elucidate the mechanisms underlying constitutive van gene expression.

Main Methods:

  • Phenotypic characterization of vancomycin and teicoplanin resistance.
  • Analysis of the vanD gene cluster and associated genes (ddl, vanS(D), vanR(D)).

Related Experiment Videos

  • Conjugation experiments to assess gene transferability.
  • Enzyme activity assays for VanX(D) and VanY(D).

    • Main Results:

    • Four clinical isolates (two Enterococcus faecium, two Enterococcus faecalis) exhibited high-level vancomycin resistance.
    • These strains harbored a chromosomal vanD gene cluster.
    • Mutations were identified in the ddl housekeeping gene and the vanS(D) or vanR(D) regulatory genes, leading to constitutive van gene expression and resistance.
    • A novel mutation in vanR(D) was identified as a potential cause of constitutive van gene expression.

    Conclusions:

    • Mutations in the ddl housekeeping gene and acquired vanS(D) or vanR(D) genes are responsible for constitutive vancomycin resistance in VanD-type Enterococcus strains.
    • The study provides the first example of constitutive van gene expression driven by a mutation in the VanR transcriptional activator.
    • Understanding these mechanisms is crucial for combating vancomycin-resistant Enterococcus infections.