Two-component System VraSR Positively Modulates the Regulation of Cell-Wall Biosynthesis Pathway in Staphylococcus Aureus

Mol Microbiol. 2003 Aug;49(3):807-21. doi: 10.1046/j.1365-2958.2003.03599.x.

Abstract

DNA microarray covering the whole genome of Staphylococcus aureus strain N315 was prepared to investigate transcription profiles. The microarray analyses revealed that vancomycin induces transcription of 139 genes. Forty-six genes among them failed to be induced in the vraSR null mutant KVR. Part of the genes regulated by VraSR system is associated with cell-wall biosynthesis, such as PBP2, SgtB and MurZ. Other cell-wall synthesis inhibitors also induced VraSR, suggesting that the sensor kinase VraS responds to the damage of cell-wall structure or inhibition of cell-wall biosynthesis. Additionally, the vraSR null mutants derived from hetero- and homo-methicillin-resistant S. aureus showed significant decrease of resistance against teicoplanin, beta-lactam, bacitracin and fosfomycin but not of D-cycloserine and levofloxacin. The observation strongly indicates that VraSR constitutes a positive regulator of cell-wall peptidoglycan synthesis, and that is deeply involved in the expression of beta-lactam and glycopeptide resistance in S. aureus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacitracin / pharmacology
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / physiology*
  • Ceftizoxime / pharmacology
  • Cell Wall / metabolism*
  • DNA-Binding Proteins
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Fosfomycin / pharmacology
  • Gene Expression Profiling*
  • Gene Expression Regulation, Bacterial / drug effects
  • Imipenem / pharmacology
  • Methicillin Resistance / genetics
  • Microbial Sensitivity Tests
  • Oligonucleotide Array Sequence Analysis
  • Oxacillin / pharmacology
  • RNA, Bacterial / biosynthesis
  • RNA, Bacterial / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism*
  • Teicoplanin / pharmacology
  • Transcription, Genetic / drug effects
  • Vancomycin / pharmacology*
  • beta-Lactam Resistance / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA-Binding Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • Receptors, Cell Surface
  • VraR protein, Staphylococcus aureus
  • VraS protein, Staphylococcus aureus
  • Bacitracin
  • Fosfomycin
  • Teicoplanin
  • Vancomycin
  • Imipenem
  • Ceftizoxime
  • Oxacillin