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Rgg Coordinates Virulence Factor Synthesis and Metabolism in Streptococcus pyogenes

Division of Basic Biomedical Science, University of South Dakota College of Medicine, Vermillion, South Dakota 57069,¹ Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,² Department of Molecular and Cell Biology, The University of Texas at Dallas, Richardson, Texas 75083³

Received 10 April 2003/ Accepted 28 July 2003

Streptococcus pyogenes is a human-specific pathogen that relies on its host for metabolic substrates. Rgg-like proteins constitute a family of transcriptional regulators present in several gram-positive bacteria. In S. pyogenes, Rgg influences the expression of several virulence-associated proteins localized to the cell wall and extracellular environment. Secreted enzymes may degrade host macromolecules, thereby liberating metabolic substrates. To determine if Rgg regulation of exoprotein expression is associated with altered metabolism, the catabolic activities of S. pyogenes strain NZ131 (serotype M49) and an isogenic rgg mutant strain were analyzed during growth with complex and defined media. As expected, the wild-type strain preferentially used glucose and produced lactic acid during the exponential phase of growth. In contrast, the rgg mutant fermented arginine in the exponential phase of growth, even in the presence of glucose. Arginine degradation was associated with a neutral culture pH and excretion of NH₃ and ornithine. Arginine, serine, and asparagine were depleted from mutant cultures during growth. The addition of arginine and serine to culture media increased the growth yield and NH₃ production of mutant but not wild-type cultures. Addition of asparagine had no effect on the growth yield of either strain. Altered metabolism of arginine and serine in the mutant was associated with increased transcript levels of genes encoding arginine deiminase and a putative serine dehydratase. Thus, Rgg coordinates virulence factor synthesis and catabolic activity and may be important in the pathogen's adaptation to changes in the availability of metabolic substrates.

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