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 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 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 (28.7 %), emm12 (24.9 %) and emm22 (7.7 %) in throat and emm1 (22 %), emm12 (10 %), emm76 (18 %) and emm49 (7 %) in skin. While all emm1 isolates were the M1UK lineage, the comparison with 2016-2017 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. 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.

Genomic Characterization of Skin and Soft Tissue Streptococcus pyogenes Isolates from a Low-Income and a High-Income Setting.

Streptococcus pyogenes is a leading cause of human morbidity and mortality, especially in resource-limited settings. The development of a vaccine against S. pyogenes is a global health priority to reduce the burden of postinfection rheumatic heart disease. To support this, molecular characterization of circulating S. pyogenes isolates is needed. We performed whole-genome analyses of S. pyogenes isolates from skin and soft tissue infections in Sukuta, The Gambia, a low-income country (LIC) in West Africa where there is a high burden of such infections. To act as a comparator to these LIC isolates, skin infection isolates from Sheffield, United Kingdom (a high-income country [HIC]), were also sequenced. The LIC isolates from The Gambia were genetically more diverse (46 emm types in 107 isolates) than the HIC isolates from Sheffield (23 emm types in 142 isolates), with only 7 overlapping emm types. Other molecular markers were shared, including a high prevalence of the skin infection-associated emm pattern D and the variable fibronectin-collagen-T antigen (FCT) types FCT-3 and FCT-4. Fewer of the Gambian LIC isolates carried prophage-associated superantigens (64%) and DNases (26%) than did the Sheffield HIC isolates (99% and 95%, respectively). We also identified streptococcin genes unique to 36% of the Gambian LIC isolates and a higher prevalence (48%) of glucuronic acid utilization pathway genes in the Gambian LIC isolates than in the Sheffield HIC isolates (26%). Comparison to a wider collection of HIC and LIC isolate genomes supported our findings of differing emm diversity and prevalence of bacterial factors. Our study provides insight into the genetics of LIC isolates and how they compare to HIC isolates. IMPORTANCE The global burden of rheumatic heart disease (RHD) has triggered a World Health Organization response to drive forward development of a vaccine against the causative human pathogen Streptococcus pyogenes. This burden stems primarily from low- and middle-income settings where there are high levels of S. pyogenes skin and soft tissue infections, which can lead to RHD. Our study provides much needed whole-genome-based molecular characterization of isolates causing skin infections in Sukuta, The Gambia, a low-income country (LIC) in West Africa where infection and RHD rates are high. Although we identified a greater level of diversity in these LIC isolates than in isolates from Sheffield, United Kingdom (a high-income country), there were some shared features. There were also some features that differed by geographical region, warranting further investigation into their contribution to infection. Our study has also contributed data essential for the development of a vaccine that would target geographically relevant strains.