Retracing the evolutionary history of the pandemic group A streptococcal M1T1 clone

The last 50 years has witnessed the emergence of new viral and bacterial pathogens with global impact on human health. The hyperinvasive group A streptococcus (GAS) M1T1 clone, was first detected in the mid-1980s in the Rocky Mountains region of the USA, has since disseminated worldwide, and remains a major cause of severe invasive human infections. While much is understood regarding the capacity of this pathogen to cause disease, much less is known of the precise evolutionary events selecting for its emergence. We used high-throughput technologies to sequence a WHO strain collection of serotype M1 GAS and reconstructed its phylogeny based on the analysis of core genome single nucleotide polymorphisms. We demonstrate that acquisition of a 36 kilobase genome segment from serotype M12 GAS and the bacteriophage-encoded DNase Sda1 led to increased virulence of the M1T1 precursor and occurred relatively early in the molecular evolutionary history of this strain. The more recent acquisition of the phage-encoded superantigen SpeA is likely to have provided selection advantage for the global dissemination of the M1T1 clone. This study provides an exemplar for the evolution and emergence of virulent clones from microbial populations existing commensally or causing only superficial infection.