A new oxidative sensing and regulation pathway mediated by the MgrA homologue SarZ in Staphylococcus aureus.
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.
Chen
Peng R
PR
Department of Chemistry, 929 East 57th Street, The University of Chicago, Chicago, IL, USA.
Nishida
Satoshi
S
Poor
Catherine B
CB
Cheng
Alice
A
Bae
Taeok
T
Kuechenmeister
Lisa
L
Dunman
Paul M
PM
Missiakas
Dominique
D
He
Chuan
C
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D012329:RNA, Bacterial / Q000235:genetics; D017384:Sequence Deletion; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D012329:RNA, Bacterial; C534537:SarZ protein, Staphylococcus aureus; D013438:Sulfhydryl Compounds; D014157:Transcription Factors