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Molecular characterization of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022-2023 UK upsurge
Jennifer N Hall1,2,3,4, Saikou Y Bah2,3,4, Henna Khalid2,3
1Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
Abstract:
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.
Insights
During 2022-2023, an increase in scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA) was observed. Genome sequencing of non-invasive StrepA isolates revealed diverse lineages, not a single genotype, contributing to the upsurge.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA) were reported in the UK during late 2022 and early 2023.
- Streptococcus pyogenes, also known as group A Streptococcus, is a significant bacterial pathogen responsible for a range of infections.
Purpose of the Study:
- To investigate the genomic diversity and characteristics of non-invasive Streptococcus pyogenes isolates during a period of increased disease incidence.
- To compare current isolates with historical data to identify changes in strain types and potential drivers of the upsurge.
Main Methods:
- Collection and whole-genome sequencing of 341 non-invasive throat and skin Streptococcus pyogenes isolates from Sheffield.
- Comparison of 2022-2023 isolate data with a 2016-2017 collection of 165 isolates.
- Analysis of emm-types, lineage diversity, capsule locus, and predicted NADase and streptolysin O (SLO) expression.
Main Results:
- Throat-associated isolates peaked in December 2022, aligning with the scarlet fever surge, while skin infections peaked later.
- The most common emm-types in 2022-2023 were emm1, emm12, and emm22 (throat) and emm1, emm12, emm76, and emm49 (skin).
- While emm1 isolates belonged to the M1_UK lineage, diverse lineages were observed in other emm-types, including a new acapsular emm75 lineage, indicating the upsurge wasn't driven by a single genotype.
- A higher proportion of skin isolates (78%) were predicted to produce capsule compared to throat isolates (51%).
- Ninety percent of throat isolates were predicted to have high NADase and SLO expression, versus 56% of skin isolates.
Conclusions:
- The Streptococcus pyogenes upsurge was characterized by diverse emm-types and emergent lineages, not solely a single dominant genotype.
- Analysis of non-invasive isolates is valuable for understanding tissue tropisms and genomic changes.
- Identifying changing strain diversity and genomic features is crucial for predicting invasive disease potential and future StrepA outbreaks.
