ERP144403 PRJEB59354 3548ec8c-be62-4459-9866-e43e0bd46d24 Genome sequence of the emm1 S. pyogenes strain S126 Streptococcus pyogenes, also known as group A Streptococcus, causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections. We characterized a pair of emm1 strains, S119 and S126, corresponding to an invasive and a carriage strain, respectively, originating from an infectious cluster. We previously reported the sequence of the S119 strain (PRJEB27939). To identify possible causes of colonization to invasive switches, here we have determined the genomic sequence of the S126 strain. Relatively to S119, the S126 strain displayed a single nucleotide difference in covS, encoding the sensor histidine kinase of the two-component CovRS system that controls the expression of 15% of the genome. In contrast with already described cases where the invasive strains harbor non-functional CovS proteins, the carriage strain possessed the mutation covST115C, leading to the replacement of the tyrosine in position 39 by a histidine, which affects the expression of the genes from the CovR regulon in a unique fashion and decreases the strain virulence in murine models of infection. Genome sequence of S. pyogenes strain S126 Streptococcus pyogenes, also known as group A Streptococcus, causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections. We characterized a pair of emm1 strains, S119 and S126, corresponding to an invasive and a carriage strain, respectively, originating from an infectious cluster. We previously reported the sequence of the S119 strain (PRJEB27939). To identify possible causes of colonization to invasive switches, here we have determined the genomic sequence of the S126 strain. Relatively to S119, the S126 strain displayed a single nucleotide difference in covS, encoding the sensor histidine kinase of the two-component CovRS system that controls the expression of 15% of the genome. In contrast with already described cases where the invasive strains harbor non-functional CovS proteins, the carriage strain possessed the mutation covST115C, leading to the replacement of the tyrosine in position 39 by a histidine, which affects the expression of the genes from the CovR regulon in a unique fashion and decreases the strain virulence in murine models of infection. ENA-FIRST-PUBLIC 2023-04-30 ENA-LAST-UPDATE 2023-04-30