A new oxidative sensing and regulation pathway mediated by the MgrA homologue SarZ in Staphylococcus aureus

Mol Microbiol. 2009 Jan;71(1):198-211. doi: 10.1111/j.1365-2958.2008.06518.x. Epub 2008 Nov 5.


Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses from the human pathogen Staphylococcus aureus. Among these, a thiol-based oxidation sensing pathway through a global regulator MgrA controls the virulence and antibiotic resistance of the bacterium. Herein, we report a new thiol-based oxidation sensing and regulation system that is mediated through a parallel global regulator SarZ. SarZ is a functional homologue of MgrA and is shown to affect the expression of approximately 87 genes in S. aureus. It uses a key Cys residue, Cys-13, to sense oxidative stress and to co-ordinate the expression of genes involved in metabolic switching, antibiotic resistance, peroxide stress defence, virulence, and cell wall properties. The discovery of this SarZ-mediated regulation, mostly independent from the MgrA-based regulation, fills a missing gap of oxidation sensing and response in S. aureus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress*
  • RNA, Bacterial / genetics
  • Sequence Deletion
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / metabolism
  • Sulfhydryl Compounds / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Bacterial Proteins
  • RNA, Bacterial
  • SarZ protein, Staphylococcus aureus
  • Sulfhydryl Compounds
  • Transcription Factors