Integrative genomic, virulence, and transcriptomic analysis of emergent <i>Streptococcus dysgalactiae</i> subspecies <i>equisimilis</i> (SDSE) <i>emm</i> type <i>stG62647</i> isolates causing human infections

This study integrated genomic sequencing, mouse virulence assays, and bacterial transcriptomic analysis to advance our understanding of the molecular mechanisms contributing to <i>Streptococcus dysgalactiae</i> subsp. <i>equisimilis emm</i> type <i>stG62647</i> pathogenesis. We tested a large cohort of genetically closely related <i>stG62647</i> isolates for virulence using an established mouse model of necrotizing myositis and discovered a broad spectrum of virulence phenotypes, with near-mortality rates ranging from 20% to 95%. This variation was unexpected, given their close genetic proximity. Transcriptome analysis of <i>stG62647</i> isolates responsible for the lowest and highest near-mortality rates suggested that these isolates used multiple molecular pathways to alter their virulence. In addition, some genes encoding transcriptional regulators and putative virulence factors likely contribute to SDSE <i>emm</i> type <i>stG62647</i> pathogenesis. These data underscore the complexity of pathogen-host interactions in an emerging SDSE clonal group.