Comparison of pharyngeal and invasive isolates of <i>Streptococcus pyogenes</i> by whole-genome sequencing in Toronto, Canada
Bibliographic record
Abstract
ABSTRACT Invasive Group A streptococcal (iGAS) infections are rising in Canada and wordwide. The 2022–2023 Ontario iGAS season was among the highest recorded, a trend continuing in 2023–2024. We sequenced 38 invasive (blood) and 117 non-invasive (pharyngeal) Streptococcus pyogenes clinical isolates from Toronto (January–May 2023) to compare between the two cohorts and against published sequences to determine if any genomic changes accounted for the trend. Results demonstrated limited clustering with one small totally invasive cluster ( emm 49) with both invasive and non-invasive isolates represented across a diverse set of lineages. Non-invasive isolates were predominantly emm12 (70.1%), whereas invasive isolates included emm 12 (26.32%), emm49 (23.68%), and emm1 (13.16%) with most emm1 strains containing the 27 SNPs that define the hypervirulent M1 UK clone (58.33%). Although there were no differences in the presence of overall virulence factors/adhesin genes between cohorts, there were statistically more superantigen and DNase genes in non-invasive isolates and a rare phage gene was significantly associated with invasiveness across three emm -types. The prevalence of individual virulence factor/adhesin genes also differed between our cohorts, including a higher likelihood of speA , enn , mrp , ideS/Mac , fbaA , and fbaB in invasive isolates. There were also no significant differences across the 11 antimicrobial resistance genes identified. Finally, pharyngeal isolates had larger hydrolysis and hemolysis zones, and covS deletions were observed in only seven invasive strains. Despite there being no genetic signature that differentiated our isolates, we observed several features that were predominant in invasive strains which provides further insights into the factors that contribute to GAS invasiveness. IMPORTANCE Increasing rates of invasive Group A streptococcal (iGAS) infections are being seen both in Canada and worldwide, which is leading to a greater disease burden caused by this pathogen. Leveraging whole-genome sequencing gives us an opportunity to better understand the underlying genetic mechanisms of streptococcal disease. By utilizing this technique, we shed light on the circulating invasive and non-invasive strains of Streptococcus pyogenes in the largest urban area in Canada from January to May 2023. GAS strains causing non-invasive disease were found to have a higher abundance of superantigen and DNase genes, whereas invasive isolates were more likely to contain M-like protein genes, the superantigen speA , the protease ideS/Mac, and/or the fibronectin-binding proteins fbaA and fbaB . This work provides valuable insights into iGAS disease which will help with surveillance, epidemiology as well as developing treatment and preventative modalities to help curb the disease burden caused by this globally important pathogen.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".