title: Mechanisms of glycopeptide resistance in enterococci.
abstract: Inducible resistance to high levels of glycopeptide antibiotics in clinical isolates of enterococci is mediated by Tn1546 or related transposons. Tn1546 encodes the VanH dehydrogenase which reduces pyruvate to D-lactate (D-Lac) and the VanA ligase which catalyses synthesis of the depsipeptide D-alanyl-D-lactate (D-Ala-D-Lac). The depsipeptide replaces the dipeptide D-Ala-D-Ala leading to production of peptidoglycan precursors which bind glycopeptides with reduced affinity. In addition, Tn1546 encodes the VanX dipeptidase and the VanY D,D-carboxypeptidase that hydrolyse the dipeptide D-Ala-D-Ala and the C-terminal D-Ala residue of the cytoplasmic precursor UDP-MurNAC-L-Ala-gamma-D- Glu-L-Lys-D-Ala-D-Ala, respectively. These two proteins act in series to eliminate D-Ala-D-Ala-containing precursors. VanX is required for resistance whereas VanY only slightly increases the level of resistance mediated by VanH, VanA and VanX.
authors.affiliation: Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Arthur
authors.forename: P E
authors.initials: PE
authors.lastname: Reynolds
authors.forename: F
authors.initials: F
authors.lastname: Depardieu
authors.forename: S
authors.initials: S
authors.lastname: Evers
authors.forename: S
authors.initials: S
authors.lastname: Dutka-Malen
authors.forename: R
authors.initials: R
authors.lastname: Quintiliani
authors.forename: P
authors.initials: P
authors.lastname: Courvalin
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004251:DNA Transposable Elements; D004352:Drug Resistance, Microbial / Q000235:genetics; D016983:Enterococcus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D014640:Vancomycin