Streptococcus pyogenes is a leading bacterial cause of human morbidity and mortality. Virulence correlates with the expression of a variety of toxins and other proteins, many of which are regulated by the transcriptional regulator Rgg1; one of four Rgg paralogues in the S. pyogenes chromosome. The Rgg1 regulon varies among clinical isolates, which differ primarily in the number and types of prophages and other horizontally transmitted elements present in chromosome. The overall hypothesis of the project is that Rgg1 interacts with specific prophage DNA to influence genomewide patterns of expression and create phenotypic diversity within the species. Such diversity is likely reflected in the wide variety of clinical manifestations associated with the pathogen. The hypothesis will be tested by characterizing Rgg1-mediated gene regulation using a genetic derivative isolate that lacks a single chromosomal island.