What question did this study set out to answer?

To investigate the virulence characteristics of the pandemic M1 UK sublineage of Streptococcus pyogenes compared to the M1 global strain.

February 11, 2026Infection and Immunity0 citationsOpen Access

Acquisition of toxin-encoding lysogenic bacteriophage elements enhances the virulence of pandemic Streptococcus pyogenes M1 UK

JDJuan Manuel DíazWestern University JWJasmine E J WellsThe University of Queensland AMAmanda C. MarpleWestern University

Key Points

To investigate the virulence characteristics of the pandemic M1 UK sublineage of Streptococcus pyogenes compared to the M1 global strain.
Obtained Canadian M1 UK isolates and sequenced genomes.
Conducted functional experiments on selected Streptococcus pyogenes strains.
Analyzed exoprotein profiles for superantigen production.
Used a HLA-transgenic mouse model for infection studies.
M1 UK strains produced significantly higher levels of SpeA superantigen compared to the M1 global strain.
Strains with additional prophage elements showed enhanced activation of human T cells.
The covS mutant and specific prophage strains led to increased severity in mouse skin infection models.

Abstract

ABSTRACT Multiple countries have observed an alarming increase in scarlet fever cases, and invasive infections often associated with a new sublineage of Streptococcus pyogenes known as M1 UK . M1 UK strains express increased levels of the streptococcal pyrogenic exotoxin A (SpeA) superantigen, and here we compare the virulence characteristics of this sublineage with the circulating M1 global strain. We obtained contemporary Canadian M1 UK isolates, and genome sequencing revealed that some M1 UK strains had acquired additional DNAse- and superantigen-encoding prophage elements, as well as an isolate with a mutation in covS . Five S . pyogenes strains were chosen for functional experiments, including 5448 (M1 global strain), M1 UK 350 (a “typical” M1 UK strain), M1 UK 162 (M1 UK strain containing a mutation in the covS gene), M1 UK 362 ΦSP1380.vir (M1 UK strain containing a prophage element encoding the spd1 , speC , and ssa genes), and M1 UK 155 Φ370.1 (M1 UK strain containing a prophage element encoding the spd1 and speC genes). Exoprotein profiles demonstrated that all M1 UK background strains had enhanced production of the SpeA superantigen relative to S. pyogenes 5448. Furthermore, strains that had acquired the additional prophage elements showed enhanced activation for human T cells, although cytotoxic activity, adhesion capacity, and DNA degradation were not detectably different. Using a “humanized” superantigen-sensitive HLA-transgenic mouse infection model, the M1 UK 162 covS mutant, and both M1 UK 362 ΦSP1380.vir and M1 UK 155 Φ370.1 strains each demonstrated increased severity during experimental skin infection compared to 5448 and M1 UK 350. These findings indicate that circulating M1 UK background strains continue to acquire additional prophage-encoded virulence factors, or hypervirulent covS mutations, and that these genetic alterations may contribute to increase severity of human infections.

Demander à l'IA

Bookmark

View Full Paper