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Characterization of emergent toxigenic M1UK Streptococcus pyogenes and associated sublineages
Ho Kwong Li1,2, Xiangyun Zhi1,2, Ana Vieira1,2
1Department of Infectious Disease, Imperial College London, London, UK.
Abstract:
Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of 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 characterize 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 phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA 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 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four 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, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs 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 M123SNPs 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.
Insights
The M1UK sublineage of Streptococcus pyogenes, defined by 27 SNPs, has become dominant due to adaptive genetic changes. This includes increased SpeA toxin production and altered carbohydrate metabolism, contributing to its success.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Streptococcus pyogenes emm1 is a globally successful and virulent clone.
- The M1UK sublineage, characterized by 27 single nucleotide polymorphisms (SNPs), has emerged as dominant in England, associated with increased scarlet fever and invasive infections.
- Understanding the genetic and molecular basis of M1UK's success is crucial for public health.
Purpose of the Study:
- To comparatively analyze the transcriptomic and proteomic profiles of the M1UK sublineage against contemporary non-M1UK emm1 strains (M1global).
- To investigate the genetic underpinnings of M1UK's dominance and increased virulence.
- To explore the evolutionary trajectory and adaptive landscape of the M1UK clone.
Main Methods:
- Comparative transcriptomic and proteomic analyses of M1UK and M1global strains.
- Phylogenetic analysis to identify intermediate emm1 sublineages.
- Gene deletion experiments to assess the role of glycerol dehydrogenase (gldA).
- Proteomic analysis of invasive strains from different phylogenetic emm1 groups.
Main Results:
- M1UK exhibited differential expression of seven genes compared to M1global, including upregulation of speA and genes in the glycerol dehydrogenase operon (gldA, mipB/talC, pflD) and downregulation of aquaporin (glpF2).
- M1UK strains possess a stop codon in gldA; deletion of gldA in M1global recapitulated operon upregulation, suggesting feedback regulation.
- Phylogenetic analysis revealed intermediate sublineages (M113SNPs and M123SNPs) that failed to expand. Proteomic analysis showed sublineage-specific changes in metabolism and protein processing.
- SpeA expression was significantly upregulated (~10-fold) in M123SNPs and M1UK in rich broth, but not in chemically defined medium.
Conclusions:
- The emergence of M1UK is attributed to the stepwise accumulation of adaptive SNPs.
- While increased SpeA production is a key feature, M1UK's competitive advantage over other emm types suggests broader fitness enhancements.
- The findings suggest that accumulated adaptive mutations confer a significant fitness advantage to M1UK on a successful emm1 streptococcal background.
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