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

Abstract

AbstractAt the end of 2022 into early 2023 the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused byStreptococcus pyogenes(StrepA or group AStreptococcus). During this time, we collected and genome sequenced 341 non-invasive throat and skinS. pyogenesisolates 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 commonemm-types in 2022-23 wereemm1 (28.7%),emm12 (24.9%), andemm22 (7.7%) in throat; andemm1 (22%),emm12 (10%),emm76 (18%), andemm49 (7%) in skin. Whilst allemm1 isolates were the M1UKlineage, comparison with 2016-17 revealed diverse lineages in otheremm-types, includingemm12, and emergent lineages within other types including a new acapsularemm75 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 futureS. pyogenesupsurges.Data summaryAll new genome sequence data is available on the NCBI short read archive under the bioproject PRJNA1062601 and individual accession numbers are listed inSupplementary Table 1 and Table 2.Impact statementThe human bacterial pathogenStreptococcus pyogenes, also known as group AStreptococcusor StrepA, caused a dramatic and sudden upsurge in scarlet fever in the UK at the end of 2022 into early 2023. We present molecular characterisation of this upsurge, through genome sequence analysis of throat, skin and other types of non-severe infection isolates collected by the microbiology diagnostic lab at the Northern General Hospital in Sheffield, England. We found that, whilst two strain types were the predominant cause of infections during the upsurge, other types had emerged or changed when compared to a similar collection from 2016-17. We also identified differences between throat-associated isolates and skin-associated isolates and highlighted important bacterial factors that might influence infection types. Isolates from non-severe throat/skin types of infections are rarely saved and therefore our knowledge of them is limited. However, here we demonstrate that study of such isolates may be key to understanding upsurges of more severe infections.