{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:23:23Z","timestamp":1788621803523,"version":"build-2803163510"},"reference-count":44,"publisher":"Microbiology Society","issue":"4","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/P022669\/1"],"award-info":[{"award-number":["MR\/P022669\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,24]]},"abstract":"\n \n \n Streptococcus pyogenes<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>\n genotype\n emm<\/jats:italic>\n 1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An\n emm<\/jats:italic>\n 1 sublineage, M1\n UK<\/jats:sub>\n , 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\n UK<\/jats:sub>\n is now dominant in England. To more fully characterize M1\n UK<\/jats:sub>\n , we undertook comparative transcriptomic and proteomic analyses of M1\n UK<\/jats:sub>\n and contemporary non-M1\n UK<\/jats:sub>\n emm<\/jats:italic>\n 1 strains (M1\n global<\/jats:sub>\n ). Just seven genes were differentially expressed by M1\n UK<\/jats:sub>\n compared with contemporary M1\n global<\/jats:sub>\n strains. In addition to\n speA<\/jats:italic>\n , five genes in the operon that includes glycerol dehydrogenase were upregulated in M1\n UK<\/jats:sub>\n (\n gldA, mipB\/talC, pflD<\/jats:italic>\n , and phosphotransferase system IIC and IIB components), while aquaporin (\n glpF2<\/jats:italic>\n ) was downregulated. M1\n UK<\/jats:sub>\n strains have a stop codon in\n gldA<\/jats:italic>\n . Deletion of\n gldA<\/jats:italic>\n in M1\n global<\/jats:sub>\n abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes\n gldA<\/jats:italic>\n , consistent with a feedback effect. Phylogenetic analysis identified two intermediate\n emm<\/jats:italic>\n 1 sublineages in England comprising 13\/27 (M1\n 13SNPs<\/jats:sub>\n ) and 23\/27 SNPs (M1\n 23SNPs<\/jats:sub>\n ), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic\n emm<\/jats:italic>\n 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\n 23SNPs<\/jats:sub>\n and M1\n UK<\/jats:sub>\n sublineages, compared with M1\n 13SNPs<\/jats:sub>\n and M1\n global<\/jats:sub>\n . We conclude that stepwise accumulation of SNPs led to the emergence of M1\n UK<\/jats:sub>\n . While increased expression of SpeA is a key indicator of M1\n UK<\/jats:sub>\n and undoubtedly important, M1\n UK<\/jats:sub>\n strains have outcompeted M1\n 23SNPs<\/jats:sub>\n and other\n emm<\/jats:italic>\n 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\n UK<\/jats:sub>\n on an inherently successful\n emm<\/jats:italic>\n 1 streptococcal background.\n <\/jats:p>","DOI":"10.1099\/mgen.0.000994","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T12:16:50Z","timestamp":1682338610000},"source":"Crossref","is-referenced-by-count":34,"title":["Characterization of emergent toxigenic M1UK\n Streptococcus pyogenes and associated sublineages"],"prefix":"10.1099","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-5943","authenticated-orcid":false,"given":"Ho Kwong","family":"Li","sequence":"first","affiliation":[{"name":"MRC Centre for Molecular Bacteriology & Infection (CMBI), Imperial College London, London, UK"},{"name":"Department of Infectious Disease, Imperial College London, London, 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