Molecular characterization of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022-2023 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 genomesequenced 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 to 2017. 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 2022-2023 were emm1 1 (28.7%), emm 12 (24.9 %) and emm 22 (7.7 %) in throat and emm1 1 (22%), emm 12 (10%), emm 76 (18 %) and emm 49 (7 %) in skin. While all emm1 1 isolates were the M1UK UK lineage, the comparison with 2016-2017 revealed diverse lineages in other emm-types, including emm 12, and emergent lineages within other types including a new acapsular emm 75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non- invasive isolates to characterize 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.