title: vanE gene cluster of vancomycin-resistant Enterococcus faecalis BM4405.
abstract: Acquired VanE-type resistance to low levels of vancomycin (MIC = 16 microg/ml) in Enterococcus faecalis BM4405 is due to the inducible synthesis of peptidoglyean precursors terminating in D-alanine-D-serine (Fines,M., B. Prichon, P. Reynolds, D. Sahm, and P. Courvalin, Antimicrob. Agents Chemother. 43:2161-2164, 1999). A chromosomal location was assigned to the vanE operon by pulsed-field gel electrophoresis and hybridization, and its sequence was determined. Three genes, encoding the VanE ligase, the VanXYE DD-peptidase, and the VanTE serine racemase, that displayed 43 to 53% identity with the corresponding genes in the vanC operon were found. In addition, two genes coding for a two-component regulatory system, VanRE-VanSE, exhibiting 60 and 44% identity with VanR,-VanS, were present downstream from vanTE. However, because of a stop codon at position 78, VanSE was probably not functional. The five genes, with the same orientation, were shown to be cotranscribed by Northern analysis and reverse transcription-PCR. The vanE, vanXYE, and vanTE genes conferred inducible low-level resistance to vancomycin after cloning in E. faecalis JH2-2, probably following cross talk with a two-component regulatory system of the host.
authors.affiliation: Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: Lorena
authors.initials: L
authors.lastname: Abadía Patiño
authors.forename: Patrice
authors.initials: P
authors.lastname: Courvalin
authors.forename: Bruno
authors.initials: B
authors.lastname: Perichon
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D019998:Racemases and Epimerases / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D015534:Trans-Activators; D014640:Vancomycin; D002268:Carboxypeptidases; D010450:Endopeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C117912:VanY protein, Bacteria; C091956:VanX dipeptidase; D019998:Racemases and Epimerases; C469909:VanT(E) protein, Enterococcus faecalis; D008025:Ligases; C469907:VanE protein, Enterococcus faecalis