Dominance of M1UK clade among Dutch M1 Streptococcus pyogenes

Rümke, Lidewij W; Gier, Brechje de; Vestjens, Stefan M T; Ende, Arie van der; Sorge, Nina M. van; Vlaminckx, Bart J. M.; Witteveen, Sandra; Santen, Marga van; Schouls, Leo M.; Kuijper, Ed J.

doi:10.1016/s1473-3099(20)30278-4

Cited by 27 publications

(25 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The emergence of the M1 UK lineage in the UK and its detection in other countries 19,[21][22][23] triggered our investigation of 318 Australian emm1 S. pyogenes isolates. Overall 310/318 were invasive isolates from sterile body sites and sourced from state-based public health laboratories in Queensland and Victoria between 2005 and 2020.…”

Section: Detection Of Streptococcus Pyogenes M1 Uk In Australiamentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

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.

show abstract

Section: Detection Of Streptococcus Pyogenes M1 Uk In Australiamentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Despite differing from older emm 1 strains by just 27 core genome SNPs, the new sublineage was characterised by a ~ten-fold increase in expression and production of the superantigen SpeA. Since 2019, the M1 UK lineage has been identified elsewhere in Europe and North America (5–7).…”

Section: Introductionmentioning

confidence: 98%

Characterisation of emergent toxigenic M1_UKStreptococcus pyogenesand associated sublineages

Zhi

Vieira

et al. 2022

Preprint

View full text Add to dashboard Cite

Emm1 Streptococcus pyogenes is a successful, globally-distributed epidemic clone that is regarded as inherently invasive. An emm1 sublineage, M1UK, that expresses increased SpeA toxin, was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterise M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UK emm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and pts system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of the gldA gene in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M1_13SNPs) and 23/27 SNPs (M1_23SNPs) respectively, that had failed to expand in the population. Proteomic analysis of these four major phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically-defined medium. In rich broth however, transcription and secretion of SpeA was upregulated ~10-fold in both M1_23SNPs and M1UK sublineages, compared with M1_13SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M1_23SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SNPs has contributed to a wider fitness advantage in M1UK on an inherently successful emm1 streptococcal background.

show abstract

“…Lynskey et al (2019) showed that the toxigenic M1T1 clone (M1T1 UK ) is related to the increased incidence of invasive GAS disease in the United Kingdom. Thereafter, the M1T1 UK strain was identified in Canada, the Netherlands, and the United States (Demczuk et al, 2019;Li et al, 2020b;Rumke et al, 2020), demonstrating the possibility of clonal expansion of the M1T1 UK clone. In Taiwan, Yan et al (2000) showed that 64.3% erythromycin-resistant isolates were clindamycin-susceptible and harbored mefA before 1998.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Effects of Acquisition of the Phage-Encoded ssa Superantigen Gene in Invasive Group A Streptococcus

et al. 2021

View full text Add to dashboard Cite

The acquisition of the phage-encoded superantigen ssa by scarlet fever-associated group A Streptococcus (Streptococcus pyogenes, GAS) is found in North Asia. Nonetheless, the impact of acquiring ssa by GAS in invasive infections is unclear. This study initially analyzed the prevalence of ssa+ GAS among isolates from sterile tissues and blood. Among 220 isolates in northern Taiwan, the prevalence of ssa+ isolates increased from 1.5% in 2008–2010 to 40% in 2017–2019. Spontaneous mutations in covR/covS, which result in the functional loss of capacity to phosphorylate CovR, are frequently recovered from GAS invasive infection cases. Consistent with this, Phostag western blot results indicated that among the invasive infection isolates studied, 10% of the ssa+ isolates lacked detectable phosphorylated CovR. Transcription of ssa is upregulated in the covS mutant. Furthermore, in emm1 and emm12 covS mutants, ssa deletion significantly reduced their capacity to grow in human whole blood. Finally, this study showed that the ssa gene could be transferred from emm12-type isolates to the emm1-type wild-type strain and covS mutants through phage infection and lysogenic conversion. As the prevalence of ssa+ isolates increased significantly, the role of streptococcal superantigen in GAS pathogenesis, particularly in invasive covR/covS mutants, should be further analyzed.

show abstract

Dominance of M1UK clade among Dutch M1 Streptococcus pyogenes

Cited by 27 publications

References 3 publications

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

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

Characterisation of emergent toxigenic M1_UKStreptococcus pyogenesand associated sublineages

Incidence and Effects of Acquisition of the Phage-Encoded ssa Superantigen Gene in Invasive Group A Streptococcus

Contact Info

Product

Resources

About

Dominance of M1UK clade among Dutch M1 Streptococcus pyogenes

Cited by 27 publications

References 3 publications

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

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

Characterisation of emergent toxigenic M1UKStreptococcus pyogenesand associated sublineages

Incidence and Effects of Acquisition of the Phage-Encoded ssa Superantigen Gene in Invasive Group A Streptococcus

Contact Info

Product

Resources

About

Characterisation of emergent toxigenic M1_UKStreptococcus pyogenesand associated sublineages