title: Catalase (KatA) and alkyl hydroperoxide reductase (AhpC) have compensatory roles in peroxide stress resistance and are required for survival, persistence, and nasal colonization in Staphylococcus aureus.
abstract: Oxidative-stress resistance in Staphylococcus aureus is linked to metal ion homeostasis via several interacting regulators. In particular, PerR controls the expression of a regulon of genes, many of which encode antioxidants. Two PerR regulon members, ahpC (alkylhydroperoxide reductase) and katA (catalase), show compensatory regulation, with independent and linked functions. An ahpC mutation leads to increased H2O2 resistance due to greater katA expression via relief of PerR repression. Moreover, AhpC provides residual catalase activity present in a katA mutant. Mutation of both katA and ahpC leads to a severe growth defect under aerobic conditions in defined media (attributable to lack of catalase activity). This results in the inability to scavenge exogenous or endogenously produced H2O2, resulting in accumulation of H2O2 in the medium. This leads to DNA damage, the likely cause of the growth defect. Surprisingly, the katA ahpC mutant is not attenuated in two independent models of infection, which implies reduced oxygen availability during infection. In contrast, both AhpC and KatA are required for environmental persistence (desiccation) and nasal colonization. Thus, oxidative-stress resistance is an important factor in the ability of S. aureus to persist in the hospital environment and so contribute to the spread of human disease.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Cosgrove
authors.forename: Graham
authors.initials: G
authors.lastname: Coutts
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: John F
authors.initials: JF
authors.lastname: Kokai-Kun
authors.forename: James J
authors.initials: JJ
authors.lastname: Mond
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D050296:Microbial Viability / Q000235:genetics; D009154:Mutation; D009296:Nasal Cavity / Q000382:microbiology*; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; D002374:Catalase; D005947:Glucose