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Deficiency of the Rgg Regulator Promotes H₂O₂ Resistance, AhpCF-Mediated H₂O₂ Decomposition, and Virulence in Streptococcus pyogenes

Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland,¹ Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, FI-20520 Turku, Finland²

Received 22 November 2007/ Accepted 19 February 2008

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.

Published ahead of print on 29 February 2008.