Analysis of the Genomics and Mouse Virulence of an Emergent Clone of Streptococcus dysgalactiae Subspecies equisimilis

Streptococcus dysgalactiae subsp. equisimilis is a bacterial pathogen that is increasingly recognized as a cause of severe human infections. Much less is known about the genomics and infection pathogenesis of S. dysgalactiae subsp. equisimilis strains compared to the closely related bacterium Streptococcus pyogenes. To address these knowledge deficits, we sequenced to closure the genomes of seven S. dysgalactiae subsp. equisimilis human isolates, including six that were emm type stG62647. Recently, for unknown reasons, strains of this emm type have emerged and caused an increasing number of severe human infections in several countries. The genomes of these seven strains vary between 2.15 and 2.21 Mbp. The core chromosomes of these six S. dysgalactiae subsp. equisimilis stG62647 strains are closely related, differing on average by only 495 single-nucleotide polymorphisms, consistent with a recent descent from a common progenitor. The largest source of genetic diversity among these seven isolates is differences in putative mobile genetic elements, both chromosomal and extrachromosomal. Consistent with the epidemiological observations of increased frequency and severity of infections, both stG62647 strains studied were significantly more virulent than a strain of emm type stC74a in a mouse model of necrotizing myositis, as assessed by bacterial CFU burden, lesion size, and survival curves. Taken together, our genomic and pathogenesis data show the strains of emm type stG62647 we studied are closely genetically related and have enhanced virulence in a mouse model of severe invasive disease. Our findings underscore the need for expanded study of the genomics and molecular pathogenesis of S. dysgalactiae subsp. equisimilis strains causing human infections. IMPORTANCE Our studies addressed a critical knowledge gap in understanding the genomics and virulence of the bacterial pathogen Streptococcus dysgalactiae subsp. equisimilis. S. dysgalactiae subsp. equisimilis strains are responsible for a recent increase in severe human infections in some countries. We determined that certain S. dysgalactiae subsp. equisimilis strains are genetically descended from a common ancestor and that these strains can cause severe infections in a mouse model of necrotizing myositis. Our findings highlight the need for expanded studies on the genomics and pathogenic mechanisms of this understudied subspecies of the Streptococcus family.