Cited by 341Bacterial Genetics and BiotechnologyAntimicrobial Resistance in StaphylococcusAntibiotic Resistance in Bacteria

The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147

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Arthur, M, Molinas, C, Courvalin, P·1992·Journal of Bacteriology

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.

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Crossref · 10.1128/jb.174.8.2582-2591.1992

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  • This initial step results in ATP-dependent phosphorylation of VanR, which subsequently binds to two promoters, one upstream of vanR and the other upstream of vanH in Tn1546.

    “This initial step results in an ATP-dependent phosphorylation of the response regulator VanR, which subsequently binds to two promoters, one of them located upstream of its own gene (vanR) and the other upstream of vanH in Tn1546 (78).”

    From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [78]

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Authors
Arthur, M., Molinas, C., & Courvalin, P.
Affiliations
Institut Pasteur (FR)
Venue
Journal of Bacteriology
Published
1992-04
Volume
174
Issue
8
Pages
2582-2591
ISSN
  • 0021-9193 (ISSN-L)
  • 1098-5530
OpenAlex
W1628177336
Cited by
338
References
49
Citations by year
2026: 5 · 2025: 11 · 2024: 4 · 2023: 7 · 2022: 12 · 2021: 11 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 4 · 2014: 15 · 2013: 5 · 2012: 4
FWCI
9.85
Type
journal article
Language
en
Open access
Locations
  • Journal of Bacteriology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords
vancomycin resistance, VanX, peptidoglycan biosynthesis, transcriptional regulation, response regulator, histidine kinase, antibiotic resistance genes
MeSH terms
Amino Acid Sequence, Bacterial Proteins, Base Sequence, Cloning, Molecular, DNA Mutational Analysis, DNA, Bacterial, Drug Resistance, Microbial, Genes, Bacterial, Genes, Regulator, Molecular Sequence Data, Oligodeoxyribonucleotides, Peptidoglycan, Promoter Regions, Genetic, Protein Kinases, Transcription Factors, Transcription, Genetic, Vancomycin, Polymerase Chain Reaction, Sequence Alignment, Enterococcus faecium

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