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

Abstract

SummaryTheStreptococcus pyogenesM1UKlineage, characterised by an intrinsic ability to express SpeA toxin and defined by 27 single nucleotide polymorphisms in the core genome, dominates the population ofemm1S. pyogenesisolates 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 M1UKlineage. Production of SpeA by strains belonging to an intermediateemm1 sublineage, M123SNP, is indistinguishable from M1UKstrains. Despite this, in England at least, M1UKhas outcompeted strains from the M123SNPsublineage. We infer that the fitness of M1UKresides in additional properties that confer an advantage toS. pyogenes, underlining a need for further research. A single nucleotide polymorphism (SNP) in the ssrA leader sequence upstream ofspeAis 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 M1globalclone and the intermediate M113SNPlineage (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 andspeAmRNA 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.