Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

Abstract

A new variant of Streptococcus pyogenes serotype M1 (designated ‘M1UK’) 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 ‘M1global’ and M1UK 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 M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1UK 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 M1UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.

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

“…The M1UK lineage has also been identified elsewhere in Europe (5), North America (6, 7), and most recently in Australia, in isolates from Queensland and Victoria dating from 2013 (8), just 3 years after its first detection in England (3). While M1UK represented ~60% of Australian emm1 isolates by 2020, in England, this proportion reached 91% by 2020 (4,8). The detection of M1UK in Australia, including Queensland, underlines the ability of this lineage to spread in temperate and more tropical climates.…”

“…M1UK strains can be differentiated from strains belonging to the highly successful emm1 S. pyogenes globallydisseminated clone that emerged in the 1980's (M1global) by just 27 single nucleotide polymorphisms in the core genome (3). The M1UK lineage has also been identified elsewhere in Europe (5), North America (6, 7), and most recently in Australia, in isolates from Queensland and Victoria dating from 2013 (8), just 3 years after its first detection in England (3). While M1UK represented ~60% of Australian emm1 isolates by 2020, in England, this proportion reached 91% by 2020 (4,8).…”

“…The detection of M1UK in Australia, including Queensland, underlines the ability of this lineage to spread in temperate and more tropical climates. Of added concern are reports of strains infected with a ΦHKU488.vir-like phage, that carries both speC and ssa superantigen genes in Australia (8). To date, this phage has not been identified in emm1 strains from England, although ~10% of emm1 strains in England do possess a phage encoding speC and spd.…”

“…intermediate sublineage appears to have been outcompeted by M1UK, suggesting an added fitness advantage in M1UK strains beyond production of SpeA alone. We postulate this further adaptation may be conferred by the additional 4 SNPs that distinguish M1UK from M123SNP isolates (3 nonsynonymous SNPs and an intergenic SNP 39bp upstream of glpF2, aquaporin, expression of which is significantly reduced in M1UK) (8,9). In this report we seek to further understand the mechanisms that differentiate SpeA-producers from non-producers among emm1 S. pyogenes strains that carry the phage that encodes speA.…”

Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201

“…Of note, most reports used genomic data that were >5 years old, so a reappraisal of prevalence is needed. A recent study in Australia using data through 2020 indicated expansion of M1 UK in Queensland and Victoria ( 10 ). The authors identified acquisition of an additional phage encoding superantigen genes ssa and spec and a single-nucleotide polymorphism (SNP) implicated in SpeA upregulation in the M1 UK lineage.…”