title: An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus.
abstract: 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.
authors.affiliation: Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
authors.forename: Peng R
authors.initials: PR
authors.lastname: Chen
authors.forename: Taeok
authors.initials: T
authors.lastname: Bae
authors.forename: Wade A
authors.initials: WA
authors.lastname: Williams
authors.forename: Erica M
authors.initials: EM
authors.lastname: Duguid
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Rice
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D006861:Hydrogen Peroxide; D003545:Cysteine