Detection of Streptococcus pyogenes M1(UK) in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

A new variant of Streptococcus pyogenes serotype M1 (designated ‘M1(UK)’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes ‘M1(global)’ and M1(UK) clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1(UK) in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1(UK) sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1(UK) lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.