Pyogenic beta-haemolytic Group A, C and G Streptococci are responsible for a significant global burden of disease in humans. Streptococcal disease manifestations range from superficial (throat and skin infections) to invasive infections (including bacteraemia and necrotising fasciitis); to toxin mediated diseases (scarlet fever and streptococcal toxic shock syndrome) and immune-mediated diseases including acute rheumatic fever and acute post-streptococcal glomerulonephritis. Streptococcus pyogenes (Group A streptococci) now causes over 500,000 deaths per year, putting it in the top ten infectious disease killers globally.
Streptococcus dysgalactiae subspecies equisimilis (SDSE; predominantly Groups C and G streptococci) is a close genetic relative to S. pyogenes; colonising the same ecological niche and causing similar clinical disease manifestations and outcomes to S. pyogenes. In some regions, the incidence of invasive disease associated with SDSE infection is higher than S. pyogenes. Despite the growing concern of clinical SDSE compared to S. pyogenes, knowledge of population structure, pathogenic mechanisms and molecular epidemiology of SDSE are limited. Global population genomics enables the opportunity to address these large knowledge gaps. Therefore, we curated a global database consisting of 416 SDSE genomes, containing at least 52 emm types from across 15 countries to assess the genetic repertoire of SDSE.
We found the SDSE population structure to be genetically diverse, containing a suite of virulence factors including streptolysins, adhesins and a limited superantigen repertoire. Furthermore, pangenome comparisons were conducted with a global S. pyogenes database consisting of 2,083 genomes, with 15 % considered shared genetic content (core) between the two species. Of this we have explored the potential contribution of lateral gene transfer and mobile genetic elements. Finally, the carriage of leading S. pyogenes vaccine antigens is assessed, providing insights into theoretical cross-species vaccine protection. Together, these findings provide insights into expanding the molecular epidemiology and biology of Group A, C and G beta-haemolytic streptococci and will ultimately assist in the management of streptococcal disease globally.