title: The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147.
abstract: Plasmid pIP816 of Enterococcus faecium BM4147 confers inducible resistance to vancomycin and encodes the VanH dehydrogenase and the VanA ligase for synthesis of depsipeptide-containing peptidoglycan precursors which bind the antibiotic with reduced affinity. We have characterized a cluster of five genes of pIP816 sufficient for peptidoglycan synthesis in the presence of vancomycin. The distal part of the van cluster encodes VanH, VanA, and a third enzyme, VanX, all of which are necessary for resistance. Synthesis of these enzymes was regulated at the transcriptional level by the VanS-VanR two-component regulatory system encoded by the proximal part of the cluster. VanR was a transcriptional activator related to response regulators of the OmpR subclass. VanS stimulated VanR-dependent transcription and was related to membrane-associated histidine protein kinases which control the level of phosphorylation of response regulators. Analysis of transcriptional fusions with a reporter gene and RNA mapping indicated that the VanR-VanS two-component regulatory system activates a promoter used for cotranscription of the vanH, vanA, and vanX resistance genes.
authors.affiliation: Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Arthur
authors.forename: C
authors.initials: C
authors.lastname: Molinas
authors.forename: P
authors.initials: P
authors.lastname: Courvalin
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects / Q000201:enzymology*; D005798:Genes, Bacterial; D005809:Genes, Regulator; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010457:Peptidoglycan / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides; D010457:Peptidoglycan; D014157:Transcription Factors; C073902:VanR protein, bacteria; C073901:VanS protein, Enterococcus; D014640:Vancomycin; D011494:Protein Kinases