Letter abstract
Nature Chemical Biology 2, 591 - 595 (2006)
Published online: 17 September 2006 | doi:10.1038/nchembio820
An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus
Peng R Chen1, Taeok Bae2,4, Wade A Williams2, Erica M Duguid1, Phoebe A Rice3, Olaf Schneewind2 & Chuan He1
Staphylococcus aureus is a human pathogen responsible for most wound and hospital-acquired infections1, 2. The protein MgrA is both an important virulence determinant during infection and a regulator of antibiotic resistance in S. aureus3, 4, 5, 6, 7. The crystal structure of the MgrA homodimer, solved at 2.86 Å, 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 species8, 9, 10, 11, 12. Our study reveals that in S. aureus, MgrA adopts a similar mechanism but uses it to globally regulate different defensive pathways.
- Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
- Department of Microbiology, The University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA.
- Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
- Present address: Indiana University School of Medicine Northwest, 3400 Broadway, Gary, Indiana 46408, USA.
Correspondence to: Chuan He1 e-mail: chuanhe@uchicago.edu
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