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. 2025 Feb 20;231(2):e375-e384.
doi: 10.1093/infdis/jiae437.

A Rapid Molecular Detection Tool for Toxigenic M1UK Streptococcus pyogenes

Stephan Brouwer  1 , Swairindhree Das  2 , Andrew J Hayes  3 , Olivia M Bertolla  1 , Mark R Davies  3 , Mark J Walker  1 , David M Whiley  2   4 , Adam D Irwin  2   4   5 , Jacob A Tickner  2   4
Affiliations

A Rapid Molecular Detection Tool for Toxigenic M1UK Streptococcus pyogenes

Stephan Brouwer et al. J Infect Dis. .

Abstract

Background: The gradual replacement of the Streptococcus pyogenes M1global genotype by a newly emergent M1UK variant is a global public health threat warranting increased surveillance. M1UK differs from progenitor M1global genotype by 27 single-nucleotide polymorphisms and is characterized by increased speA superantigen expression in vitro.

Methods: An allele-specific real-time polymerase chain reaction assay was developed for the rapid detection of M1UK strains. The assay was used in combination with whole genome sequencing to determine emm (sub)type distribution for 51 invasive (n = 9) and noninvasive (n = 42) S pyogenes clinical isolates.

Results: Emm1 was the most prevalent S pyogenes emm serotype (n = 11) in this set of clinical isolates, with M1UK being the dominant emm1 genotype (4/5 invasive, 3/6 noninvasive isolates). The assay accurately detected M1UK strains. Whole genome sequencing revealed continued presence of Australian M1UK sublineages associated with epidemic scarlet fever-causing S pyogenes in Asia.

Conclusions: Our study establishes a suitable target for detection of the toxigenic M1UK and confirms the maintenance of M1UK strains in Queensland, Australia. This assay can be deployed in laboratories and provides a valuable, cost-effective tool to enhance surveillance of the expanding M1UK clone.

Keywords: Streptococcus pyogenes; ssrA SNP; M1UK; real-time PCR; scarlet fever.

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Conflict of interest statement

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Phylogenetic analysis of 748 global emm1 Streptococcus pyogenes. Maximum-likelihood phylogenetic tree derived from 3482 single-nucleotide polymorphism sites from a 1 626 524 bp core genome alignment relative to the 5448 M1global reference genome. The position of the 11 emm1 isolates sequenced in this study are indicated by black tips and annotated by strain name (colored by genotype: M1global [blue], M1inter [purple], and M1UK [red]). A global database of 737 emm1 isolates was used for context [23] with comparative reference isolates referred to in this study are annotated in black. Continent of isolation and clinical sample type are colored as shown in the legend. Carriage of key virulence and antimicrobial resistance determinants are indicated as per legend with probable referring to fragmented gene assemblies preventing accurate in silico prediction. Abbreviation: iGAS, invasive Group A Streptococcus.
Figure 2.
Figure 2.
Maintenance of M1UK sublineages with an extended toxin repertoire and detection of CovR A111V mutants in M1UK. A, Carriage of scarlet fever–associated toxins in 11 emm1 pharyngeal isolates was confirmed by polymerase chain reaction (PCR). B, Quantitative real-time PCR of indicated virulence genes in M1UK (SP1380, SP1511, and SP1512) versus M1global (5448) genotypes. Data from 3 biological replicates are presented as mean values ± standard error of the mean. Statistical significance was assessed using 1-way analysis of variance with Dunnett multiple comparisons post hoc test against the 5448 control group (****P < .0001, ***P < .001, **P < .01, *P < .05; ns, not significant). C, Western blot analysis of SpeA, PepO, SpeB (pro- and mature forms), and SLO in culture supernatants and SpyCEP in cell wall extracts from indicated emm1 strains grown to late-logarithmic phase of growth. D, Western blot analysis of SpeB (pro- and mature forms) in overnight culture supernatants. The Australian M1UK isolate SP1380 was used as a control [33].
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