Tricontinental detection of Streptococcus pyogenes M1UK: A call for wider research and active surveillance

The Streptococcus pyogenes M1UK lineage, characterised by an intrinsic ability to express SpeA toxin and defined by 27 single nucleotide polymorphisms in the core genome, dominates the population of emm 1 S. pyogenes isolates in England. The lineage has been identified elsewhere in Europe, North America, and, most recently, Australia. SpeA however may not be the sole deterministic factor underlying success of the M1UK lineage. Production of SpeA by strains belonging to an intermediate emm 1 sublineage, M123SNP, is indistinguishable from M1UK strains. Despite this, in England at least, M1UK has outcompeted strains from the M123SNP sublineage. We infer that the fitness of M1UK resides in additional properties that confer an advantage to S. pyogenes , underlining a need for further research. A single nucleotide polymorphism (SNP) in the ssrA leader sequence upstream of speA is one of a limited number of SNPs that distinguish intermediate sublineages that differ in SpeA production. Introduction of the ssrA SNP into representative isolates of the widely disseminated M1global clone and the intermediate M113SNP lineage (that cannot otherwise produce readily-detectable SpeA in culture) resulted in SpeA expression, confirming the importance of the ssrA SNP to SpeA phenotype. However, RNAseq analysis of clinical strains showed that presence of the SNP was not invariably linked to read-through from the ssrA leader sequence or SpeA expression. Literature review suggests that read through and speA mRNA transcript length may be impacted by the two component regulator CovRS, pointing to a complex regulatory network interaction between the bacterial chromosome and phage-encoded superantigens. ### Competing Interest Statement The authors have declared no competing interest.