Molecular characterisation of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022-23 UK upsurge

At the end of 2022 into early 2023 the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus). During this time, we collected and genome sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016-17. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm-types in 2022-23 were emm1 (28.7%), emm12 (24.9%), and emm22 (7.7%) in throat; and emm1 (22%), emm12 (10%), emm76 (18%), and emm49 (7%) in skin. Whilst all emm1 isolates were the M1UK lineage, comparison with 2016-17 revealed diverse lineages in other emm-types, including emm12, and emergent lineages within other types including a new acapsular emm75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. Analysis of the capsule locus predicted only 51% of throat isolates would produce capsule compared to 78% of skin isolates. 90% of throat isolates were also predicted to have high NADase and Streptolysin O (SLO) expression, based on the promoter sequence, compared to only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterise tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges.