An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus

Nat Chem Biol. 2006 Nov;2(11):591-5. doi: 10.1038/nchembio820. Epub 2006 Sep 17.


Staphylococcus aureus is a human pathogen responsible for most wound and hospital-acquired infections. The protein MgrA is both an important virulence determinant during infection and a regulator of antibiotic resistance in S. aureus. The crystal structure of the MgrA homodimer, solved at 2.86 A, indicates the presence of a unique cysteine residue located at the interface of the protein dimer. We discovered that this cysteine residue can be oxidized by various reactive oxygen species, such as hydrogen peroxide and organic hydroperoxide. Cysteine oxidation leads to dissociation of MgrA from DNA and initiation of signaling pathways that turn on antibiotic resistance in S. aureus. The oxidation-sensing mechanism is typically used by bacteria to counter challenges of reactive oxygen and nitrogen species. Our study reveals that in S. aureus, MgrA adopts a similar mechanism but uses it to globally regulate different defensive pathways.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cysteine / chemistry
  • Cysteine / drug effects
  • Cysteine / metabolism
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / pharmacology
  • Oxidation-Reduction
  • Protein Conformation
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Staphylococcus aureus / chemistry*
  • Staphylococcus aureus / metabolism*


  • Bacterial Proteins
  • Repressor Proteins
  • Hydrogen Peroxide
  • Cysteine

Associated data

  • PDB/2BV6
  • PubChem-Substance/14715875
  • PubChem-Substance/14715876
  • PubChem-Substance/14715877
  • PubChem-Substance/14715878
  • PubChem-Substance/14715879
  • PubChem-Substance/14715880
  • PubChem-Substance/14715881