Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Abstract

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

Overlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange

“…The sil locus was present in 235 (80%) of isolates. All 12 S. pyogenes vaccine candidate genes ( adi, fbp54, oppA, pulA, scpA, shr, slo, spy0762, spy0942, spyAD, srtA, ropA ) which were previously found in >99% of SDSE and S. pyogenes global isolates 13 were also present in all sequenced SDSE isolates from this study. Sequencing and analysis of 315/327 (96%) S. pyogenes isolates recovered from communities 1 and 3 were reported previously 17 .…”

“…Phylogenetic reconstruction supported 18 distinct SDSE lineages/global genomic sequence clusters 13 present across both communities (Fig. 1 ).…”

“… Sequences were aligned against SDSE reference genome GGS_124 (NC_012891.1) with mobile genetic element regions masked. Distinct genomic sequence clusters determined by PopPUNK 31 as previously defined by a global SDSE dataset 13 , are denoted by alternating blue and grey highlights from internal nodes. Site of isolation is coloured by blue (throat) and red (skin) tips.…”

“…Whole genome comparisons of SDSE and S. pyogenes demonstrate extensive genomic homology including shared virulence factors such as the multi-functional surface M protein and evidence of horizontal gene transfer (HGT), frequently involving mobile genetic elements (MGEs) 11 – 13 . These similarities may contribute to shared disease phenotypes.…”

“…These similarities may contribute to shared disease phenotypes. Many S. pyogenes vaccine candidates are present in both species with evidence of cross-species homologous recombination 13 .…”