Background: Streptococcus pyogenes is a human obligate pathogen with thousands of genome sequences publicly available. Population genomic analyses have revealed that S. pyogenes has a large pool of accessory genes often comprising key virulence and antimicrobial resistance genes associated with mobile genetic elements (MGE) such as prophage and integrative conjugative elements. However, we do not have a good understanding of the evolutionary contribution of the non-MGE gene content, which contribute up to 50% of the S. pyogenes accessory genome.
Method: We examined the pan-genome of S. pyogenes in the context of microevolution of S. pyogenes emm75 and within a larger global framework. Classic genomic epidemiological approaches examining emm-subtypes, MLST, core-genome clusters, and novel bioinformatic tools were used to dissect the pan-genome of S. pyogenes identifying lineages and associated evolutionary drivers.
Results: S. pyogenes emm75 revealed multiple independently evolving global lineages. Lineages carried traditional signatures of mobile genetic elements in addition to gene content not related to MGEs. eight non-mobile related accessory loci were related to metabolic functions and self-defence systems. In a global framework of S. pyogenes, a larger pool of non-mobile related accessory loci were identified with some displaying a dynamic evolutionary association indicating a wider metabolic evolutionary signature.
Conclusion: This work reveals how S. pyogenes’ evolution is driven by deeper underlying movement of accessory gene content, unrelated to traditional mobile genetic elements. This accessory gene pool may play a substantial role in the long-term evolution. Better understanding of this phenomenon could shed light on previously elusive topics in S. pyogenes’ biology and epidemiological behaviour.