title: Characterization of the vanD glycopeptide resistance gene cluster from Enterococcus faecium BM4339.
abstract: VanD-type resistance to glycopeptides in Enterococcus faecium BM4339 is due to constitutive synthesis of D-alanyl-D-lactate-terminating peptidoglycan precursors (B. Périchon, P. Reynolds, and P. Courvalin, Antimicrob. Agents Chemother. 41:2016-2018, 1997). The sequence of a 5,780-bp fragment was determined and revealed six open reading frames. The 3' distal part encoded the VanHD dehydrogenase, the VanD ligase, and the VanXD DD-dipeptidase, which were highly similar to the corresponding proteins in VanA and VanB types of resistance. The deduced VanYD protein was homologous to penicillin-binding proteins that display DD-carboxypeptidase activity. The 5' end coded for the putative VanRD-VanSD two-component regulatory system. Due to a frameshift mutation in the chromosomal ddl gene, BM4339 produced an impaired D-alanine:D-alanine ligase. However, since expression of the resistance genes is constitutive, growth of E. faecium BM4339 was not dependent on the presence of glycopeptides in the culture medium.
authors.affiliation: Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: B
authors.initials: B
authors.lastname: Casadewall
authors.forename: P
authors.initials: P
authors.lastname: Courvalin
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D002268:Carboxypeptidases; D002876:Chromosomes, Bacterial; D017124:Conserved Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics*; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D004926:Escherichia coli / Q000235:genetics; D016368:Frameshift Mutation; D005838:Genotype; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D016366:Open Reading Frames; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics; D010957:Plasmids; D016415:Sequence Alignment; D013302:Streptomyces / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; C070700:VanH protein, Enterococcus faecium; D014640:Vancomycin; D002268:Carboxypeptidases; C117912:VanY protein, Bacteria; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase