Recombination Is a Major Source of Genetic and Pathogenic Diversification of Group A Streptococcus Serotype M89 Strains.

Background: GAS(Streptococcus pyogenes)is a genetically diverse human pathogen having > 150 serotypes. Serotype M89 strains are a common cause of GAS pharyngeal and invasive infections. Recent studies indicate M89 strains may be increasing in prevalence. Over the last 15 years in Italy, two large epidemic outbreaks were caused by macrolide resistant M89 strains. M89 epidemic strains differed in gene content encoding virulence factors and macrolide resistance. We used comparative genomics to assess serotype M89 genetic diversity and its contribution to GAS pathogenesis. Methods:Next-generation DNA sequencing was conducted for 22 isolates (Italy = 5, Canada = 1, New Zealand = 1, U.S.A. = 15). Complete genomes were determined for 1 Italian and 1 U.S. strain. Polymorphisms were identified genome-wide for the cohort and used to infer genetic relationships. Results:The genome of Italian strain 11610 is 1,709,407 bp and lacks prophages. Italian epidemic isolates differed pairwise by ~32 core-genome SNPs. The genome of U.S. strain MGAS11027 is 1,786,881bp and has 2 prophages encoding secreted virulence factors. U.S. M89 strains differed pairwise by ~397 SNPs. Italian M89s differed from U.S. M89s by ~2064 SNPs. SNPs among U.S. M89s, and differing U.S. from Italian M89s, were nonrandomly clustered. Conclusions:SNPs among the M89 strains exceeded that among other GAS serotypes.Most SNPs were attributed to discrete recombination events involving genes encoding virulence factors including surface adhesins, antimicrobial peptides, and secreted anti-immune response proteins.These findings demonstrate that genetic recombination strongly contributes to diversification of M89 pathogenic capacity.