title: The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen Species Resistance via Transcriptional Regulation of Staphyloxanthin Production.
abstract: Staphylococcus aureus is an important opportunistic pathogen and is the etiological agent of many hospital- and community-acquired infections. The golden pigment, staphyloxanthin, of S. aureus colonies distinguishes it from other staphylococci and related Gram-positive cocci. Staphyloxanthin is the product of a series of biosynthetic steps that produce a unique membrane-embedded C30golden carotenoid and is an important antioxidant. We observed that a strain with an inducible airR overexpression cassette had noticeably increased staphyloxanthin production compared to the wild-type strain under aerobic culturing conditions. Further analysis revealed that depletion or overproduction of the AirR response regulator resulted in a corresponding decrease or increase in staphyloxanthin production and susceptibility to killing by hydrogen peroxide, respectively. Furthermore, the genetic elimination of staphyloxanthin during AirR overproduction abolished the protective phenotype of increased staphyloxanthin production in a whole-blood survival assay. Promoter reporter and gel shift assays determined that the AirR response regulator is a direct positive regulator of the staphyloxanthin-biosynthetic operon, crtOPQMN, but is epistatic to alternative sigma factor B. Taken together, these data indicate that AirSR positively regulates the staphyloxanthin-biosynthetic operon crtOPQMN, promoting survival of S. aureus in the presence of oxidants.
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Hall
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA.
authors.forename: Junshu
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA.|School of Life Science, Jilin Normal University, Siping, China.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA jixxx002@umn.edu.
authors.forename: Yinduo
authors.initials: Y
authors.lastname: Ji
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation; D010860:Pigments, Biological / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012808:Sigma Factor / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D024341:Xanthophylls / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D010860:Pigments, Biological; D017382:Reactive Oxygen Species; D012808:Sigma Factor; D024341:Xanthophylls; C031841:staphyloxanthin; D006861:Hydrogen Peroxide
keywords: AirSR; S. aureus; staphyloxanthin; transcriptional regulation; two-component regulatory systems