Rapid expansion and international spread of M1 in the post-pandemic UK upsurge of Streptococcus pyogenes.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1 to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1 strains, invasive M1 strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1 is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1 clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1 isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1 point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.