title: Deficiency of the Rgg regulator promotes H2O2 resistance, AhpCF-mediated H2O2 decomposition, and virulence in Streptococcus pyogenes.
abstract: Streptococcus pyogenes (group A streptococcus [GAS]), a catalase-negative gram-positive bacterium, is aerotolerant and survives H2O2 exposures that kill many catalase-positive bacteria. The molecular basis of the H2O2 resistance is poorly known. Here, we demonstrate that serotype M49 GAS lacking the Rgg regulator is more resistant to H2O2 and also decomposes more H2O2 than the parental strain. Subgenomic transcriptional profiling and genome-integrated green fluorescent protein reporters showed that a bicistronic operon, a homolog of the Streptococcus mutans ahpCF operon, is transcriptionally up-regulated in the absence of Rgg. Phenotypic assays with ahpCF operon knockouts demonstrated that the gene products decompose H2O2 and protect GAS against peroxide stress. In a murine intraperitoneal-infection model, Rgg deficiency increased the virulence of GAS, although in an ahpCF-independent manner. Rgg-mediated repression of H2O2 resistance is divergent from the previously characterized peroxide resistance repressor PerR. Moreover, Rgg-mediated repression of H2O2 resistance is inducible by cellular stresses of diverse natures--ethanol, organic hydroperoxide, and H2O2. Rgg is thus identified as a novel sensoregulator of streptococcal H2O2 resistance with potential implications for the virulence of the catalase-negative GAS.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland. arto.pulliainen@unibas.ch
authors.forename: Arto Tapio
authors.initials: AT
authors.lastname: Pulliainen
authors.forename: Jukka
authors.initials: J
authors.lastname: Hytönen
authors.forename: Sauli
authors.initials: S
authors.lastname: Haataja
authors.forename: Jukka
authors.initials: J
authors.lastname: Finne
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009876:Operon / Q000235:genetics*; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D015534:Trans-Activators; C074779:rgg protein, Streptococcus; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins