Characterization of emergent toxigenic M1UK Streptococcus pyogenes and associated sublineages

• Published in: Microbial genomics Vol. 9; no. 4
• Main Authors: Li, Ho Kwong, Zhi, Xiangyun, Vieira, Ana, Whitwell, Harry J., Schricker, Amelia, Jauneikaite, Elita, Li, Hanqi, Yosef, Ahmed, Andrew, Ivan, Game, Laurence, Turner, Claire E., Lamagni, Theresa, Coelho, Juliana, Sriskandan, Shiranee
• Format: Journal Article
• Language: English
• Published: Microbiology Society 24.04.2023
• ISSN: 2057-5858; 2057-5858
• DOI: 10.1099/mgen.0.000994

Streptococcus pyogenes genotype emm 1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm 1 sublineage, M1 UK , 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, M1 UK is now dominant in England. To more fully characterize M1 UK , we undertook comparative transcriptomic and proteomic analyses of M1 UK and contemporary non-M1 UK emm 1 strains (M1 global ). Just seven genes were differentially expressed by M1 UK compared with contemporary M1 global strains. In addition to speA , five genes in the operon that includes glycerol dehydrogenase were upregulated in M1 UK ( gldA, mipB/talC, pflD , and phosphotransferase system IIC and IIB components), while aquaporin ( glpF2 ) was downregulated. M1 UK strains have a stop codon in gldA . Deletion of gldA in M1 global 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 emm 1 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 invasive strains from the four phylogenetic emm 1 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 M1 23SNPs and M1 UK sublineages, compared with M1 13SNPs and M1 global . We conclude that stepwise accumulation of SNPs led to the emergence of M1 UK . While increased expression of SpeA is a key indicator of M1 UK and undoubtedly important, M1 UK 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 M1 UK on an inherently successful emm 1 streptococcal background.