An oxidation sensing mechanism is used by a global regulator of Staphylococcus aureus

BIOL 91

Peng R. Chen, pengchen@uchicago.edu1, Taeok Bae2, Wade A. Williams2, Erica M. Duguid, eduguid@uchicago.edu1, Phoebe A. Rice3, Olaf Schneewind2, and Zigang Li, zgli@uchicago.edu1. (1) Department of Chemistry, The University of Chicago, 5735 S. Ellis Avenue, Chicago, IL 60637, (2) Department of Microbiology, The University of Chicago, 920 East 58th Street, Chicago, IL 60637, (3) Department of Biochemistry and Molecular Biology, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637
The protein MgrA is a major virulence determinant during infection of Staphylococcus aureus, an important human pathogen. MgrA has also been shown to be a global regulator that controls expression of ~350 different genes in S. aureus including antibiotic resistance genes. The crystal structure of MgrA homodimer, solved at 2.86 Å, indicates presence of a unique Cys residue located in the interface of the protein dimer. We subsequently discovered this Cys can be oxidized by reactive oxygen species, which leads to dissociation of MgrA from DNA and initiation of signaling pathways that turn on antibiotic resistance. The oxidation sensing mechanism is typically employed by bacteria to counter challenge of reactive oxygen species. Our study here reveals that the global regulator MgrA adopts the similar mechanism but uses it to regulate antibiotic resistance. This unique signaling mechanism may be used by other regulators in S. aureus or by other pathogens.
 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006