Identification of the up- and down-regulated genes in vancomycin-resistant Staphylococcus aureus strains Mu3 and Mu50 by cDNA differential hybridization method

Biochem Biophys Res Commun. 2000 Mar 16;269(2):485-90. doi: 10.1006/bbrc.2000.2277.


We previously reported the first vancomycin-resistant Staphylococcus aureus (VRSA) clinical strain, Mu50, whose cell wall is remarkably thickened resulting from the activation of cell-wall synthesis. To explore the genetic basis for the vancomycin resistance, cDNA differential hybridization was performed using RNAs extracted from a set of closely related S. aureus strains with various levels of vancomycin susceptibilities. The strains were Mu3 (MIC = 2 microg/ml), Mu50 (MIC = 8 microg/ml), and a susceptible revertant of Mu50, Mu50omega (MIC = 0.5 microg/ml). In this study, we report identification of a novel response regulator, designated vraR (standing for vancomycin-resistance associated gene R) whose transcription was remarkably up-regulated in Mu3 and Mu50 as compared to Mu50omega. Experimental over-expression of VraR in vancomycin-susceptible strain N315P raised vancomycin resistance of the strain. Also, the genes coding for fructose utilization, fatty acid metabolism, and two putative ATP-binding cassette (ABC) transporter genes were found to be up-regulated in Mu3 and Mu50. On the other hand, Protein A expression was suppressed in Mu50, as compared with Mu3 and Mu50omega. We consider that the response regulator vraR is one of the key regulators modulating the level of vancomycin-resistance in S. aureus. Presumed increased uptake of fructose and altered fatty acid metabolism may also contribute to vancomycin resistance by supplying more precursor metabolites for cell-wall synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Base Sequence
  • DNA Primers
  • DNA, Complementary
  • Down-Regulation*
  • Drug Resistance, Microbial / genetics
  • Genes, Bacterial
  • Nucleic Acid Hybridization
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics*
  • Up-Regulation*
  • Vancomycin / pharmacology*


  • Anti-Bacterial Agents
  • DNA Primers
  • DNA, Complementary
  • Vancomycin