Beschreibung:
<jats:title>Abstract</jats:title><jats:p><jats:italic>Streptococcus pyogenes</jats:italic> (group A <jats:italic>Streptococcus</jats:italic>; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the <jats:italic>csrS/csrR</jats:italic> (<jats:italic>covS/covR</jats:italic>) and/or <jats:italic>rgg</jats:italic> (<jats:italic>ropB</jats:italic>) genes, which are negative regulators of virulence. However, these mutations were found at somewhat low frequencies in <jats:italic>emm1</jats:italic>-genotyped isolates, the most prevalent STSS genotype. In this study, we sought to detect causal mutations of enhanced virulence in <jats:italic>emm1</jats:italic> isolates lacking mutation(s) in the <jats:italic>csrS/csrR</jats:italic> and <jats:italic>rgg</jats:italic> genes. Three mutations associated with elevated virulence were found in the <jats:italic>sic</jats:italic> (a virulence gene) promoter, the <jats:italic>csrR</jats:italic> promoter and the <jats:italic>rocA</jats:italic> gene (a <jats:italic>csrR</jats:italic> positive regulator). <jats:italic>In vivo</jats:italic> contribution of the <jats:italic>sic</jats:italic> promoter and <jats:italic>rocA</jats:italic> mutations to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the <jats:italic>sic</jats:italic> promoter mutation was significantly higher in STSS <jats:italic>emm1</jats:italic> isolates than in non-invasive STSS isolates; the <jats:italic>rocA</jats:italic> gene mutation frequency was not significantly different among STSS and non-STSS isolates. STSS <jats:italic>emm1</jats:italic> isolates possessed a high frequency mutation in the <jats:italic>sic</jats:italic> promoter. Thus, this mutation may play a role in the dynamics of virulence and STSS pathogenesis.</jats:p>