{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:21:21Z","timestamp":1787631681064,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Streptococcus pyogenes<\/jats:italic> is a bacterial pathogen that causes a wide spectrum of clinical diseases exclusively in humans. The distribution of <jats:italic>emm<\/jats:italic> type, antibiotic resistance and virulence gene expression for <jats:italic>S. pyogenes<\/jats:italic> varies temporally and geographically, resulting in distinct disease spectra. In this study, we analyzed antibiotic resistance and resistance gene expression patterns among <jats:italic>S. pyogenes<\/jats:italic> isolates from pediatric patients in China and investigated the relationship between virulence gene expression, <jats:italic>emm<\/jats:italic> type, and disease categories. Forty-two representative <jats:italic>emm<\/jats:italic>1.0 and <jats:italic>emm<\/jats:italic>12.0 strains (<jats:italic>n<\/jats:italic> = 20 and <jats:italic>n<\/jats:italic> = 22, respectively) isolated from patients with scarlet fever or obstructive sleep apnea-hypopnea syndrome were subjected to whole-genome sequencing and phylogenetic analysis. These strains were further analyzed for susceptibility to vancomycin. We found a high rate and degree of resistance to macrolides and tetracycline in these strains, which mainly expressed <jats:italic>ermB<\/jats:italic> and <jats:italic>tetM<\/jats:italic>. The disease category correlated with <jats:italic>emm<\/jats:italic> type but not superantigens. The distribution of <jats:italic>vanuG<\/jats:italic> and virulence genes were associated with <jats:italic>emm<\/jats:italic> type. Previously reported important prophages, such as \u03c6HKU16.vir, \u03c6HKU488.vir, \u03a65005.1, \u03a65005.2, and \u03a65005.3 encoding streptococcal toxin, and integrative conjugative elements (ICEs) such as ICE-emm12 and ICE-HKU397 encoding macrolide and tetracycline resistance were found present amongst <jats:italic>emm<\/jats:italic>1 or <jats:italic>emm<\/jats:italic>12 clones from Shenzhen, China.<\/jats:p>","DOI":"10.3389\/fmicb.2021.722225","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T16:06:57Z","timestamp":1639066017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Dingle","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunmei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejie","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"D517","DOI":"10.1093\/nar\/gkz935","article-title":"CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database.","volume":"48","author":"Alcock","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.4103\/ijmr.IJMR_1517_16","article-title":"Antimicrobial resistance in beta-haemolytic streptococci in India: a four-year study.","volume":"147","author":"Bhardwaj","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"B3","first-page":"1","article-title":"Toxins and superantigens of group A streptococci.","volume":"7","author":"Blake","year":"2019","journal-title":"Microbiol. Spect."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18700-5","article-title":"Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes.","volume":"11","author":"Brouwer","year":"2020","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/s1473-3099(05)70267-x","article-title":"The global burden of group A streptococcal diseases.","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1128\/iai.68.6.3523-3534.2000","article-title":"Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases.","volume":"68","author":"Chatellier","year":"2000","journal-title":"Infect. Immun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/gigascience\/gix120","article-title":"SOAPnuke: a MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data.","volume":"7","author":"Chen","year":"2018","journal-title":"Gigascience"},{"key":"B8","year":"2019"},{"key":"B9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/ng.3147","article-title":"Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance.","volume":"47","author":"Davies","year":"2015","journal-title":"Nat. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1093\/bioinformatics\/btm009","article-title":"Identifying bacterial genes and endosymbiont DNA with Glimmer.","volume":"23","author":"Delcher","year":"2007","journal-title":"Bioinformatics"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10092043","article-title":"Genital tract GAS infection ISIDOG guidelines.","volume":"10","author":"Donders","year":"2021","journal-title":"J. Clin. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3201\/eid0502.990209","article-title":"emm typing and validation of provisional M types for group A streptococci.","volume":"5","author":"Facklam","year":"1999","journal-title":"Emerg. Infect. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.diagmicrobio.2010.03.014","article-title":"Macrolide-resistant Streptococcus pyogenes from Chinese pediatric patients in association with Tn916 transposons family over a 16-year period.","volume":"67","author":"Feng","year":"2010","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: accelerated for clustering the next-generation sequencing data.","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinformatics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1080\/23744235.2019.1638964","article-title":"Relation between emm types and virulence gene profiles among Bulgarian Streptococcus pyogenes clinical isolates.","volume":"51","author":"Gergova","year":"2019","journal-title":"Infect. Dis. (Lond)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1007\/s10096-015-2414-x","article-title":"Decline in macrolide resistance rates among Streptococcus pyogenes causing pharyngitis in children isolated in Italy.","volume":"34","author":"Gherardi","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00059","article-title":"Prevalent emm Types among Invasive GAS in Europe and North America since Year 2000.","volume":"6","author":"Gherardi","year":"2018","journal-title":"Front. Public Health"},{"key":"B18","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s10096-016-2593-0","article-title":"Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections.","volume":"35","author":"Goli\u0144ska","year":"2016","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.anpedi.2019.10.014","article-title":"[Invasive Streptococcus pyogenes infections (2011-2018): emm-type and clinical presentation].","volume":"92","author":"Gonz\u00e1lez-Abad","year":"2020","journal-title":"An. Pediatr. (Engl Ed)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1128\/mSphere.00090-20","article-title":"Restricted sequence variation in streptococcus pyogenes penicillin binding proteins.","volume":"5","author":"Hayes","year":"2020","journal-title":"mSphere"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2021.05.012","article-title":"Microbiological findings of symptomatic vulvovaginitis in Chinese prepubertal girls.","author":"Hu","year":"2021","journal-title":"J. Pediatr. Adolesc. Gynecol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/s0378-1097(03)00842-5","article-title":"Identification of superantigen genes speM, ssa, and smeZ in invasive strains of beta-hemolytic group C and G streptococci recovered from humans.","volume":"229","author":"Igwe","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180757","article-title":"Epidemiology and distribution of 10 superantigens among invasive Streptococcus pyogenes disease in Germany from 2009 to 2014.","volume":"12","author":"Im\u00f6hl","year":"2017","journal-title":"PLoS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2020.104609","article-title":"Global genomic epidemiology of Streptococcus pyogenes.","volume":"86","author":"Jespersen","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.jid.2018.11.027","article-title":"Group a streptococcal DNase Sda1 impairs plasmacytoid dendritic Cells\u2019 Type 1 interferon response.","volume":"139","author":"Keller","year":"2019","journal-title":"J. Invest. Dermatol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/nar\/gkm160","article-title":"RNAmmer: consistent and rapid annotation of ribosomal RNA genes.","volume":"35","author":"Lagesen","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1007\/s10096-020-03987-5","article-title":"Epidemiological analysis of Group A Streptococcus infections in a hospital in Beijing, China.","volume":"39","author":"Li","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1099\/jmm.0.042309-0","article-title":"Epidemiological and molecular characteristics of clinical isolates of Streptococcus pyogenes collected between 2005 and 2008 from Chinese children.","author":"Liang","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.ijmm.2007.03.015","article-title":"A new closed-tube multiplex real-time PCR to detect eleven superantigens of Streptococcus pyogenes identifies a strain without superantigen activity.","volume":"297","author":"Lintges","year":"2007","journal-title":"Int. J. Med. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"D443","DOI":"10.1093\/nar\/gkn656","article-title":"ARDB\u2013antibiotic resistance genes database.","volume":"37","author":"Liu","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"D687","DOI":"10.1093\/nar\/gky1080","article-title":"VFDB 2019: a comparative pathogenomic platform with an interactive web interface.","volume":"47","author":"Liu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01052","article-title":"High prevalence of macrolide-resistance and molecular characterization of Streptococcus pyogenes isolates circulating in China from 2009 to 2016.","volume":"8","author":"Lu","year":"2017","journal-title":"Front. Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1017\/s0950268809002118","article-title":"Characterization of emm types and superantigens of Streptococcus pyogenes isolates from children during two sampling periods.","volume":"137","author":"Ma","year":"2009","journal-title":"Epidemiol. Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.1128\/iai.67.9.4307-4311.1999","article-title":"Streptococcal pyrogenic exotoxin F (SpeF) causes permeabilization of lung blood vessels.","volume":"67","author":"Matsumoto","year":"1999","journal-title":"Infect. Immun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1128\/jcm.01312-09","article-title":"Streptococcus pyogenes isolates causing severe infections in Norway in 2006 to 2007: emm types, multilocus sequence types, and superantigen profiles.","volume":"48","author":"Meisal","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1017\/s0950268802006854","article-title":"Distribution of emm genotypes and superantigen genes of Streptococcus pyogenes isolated in Japan, 1994-9.","volume":"128","author":"Murakami","year":"2002","journal-title":"Epidemiol. Infect."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e1993","DOI":"10.1128\/jcm.01993-19","article-title":"Reduced in vitro susceptibility of streptococcus pyogenes to \u03b2-Lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread.","volume":"58","author":"Musser","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1128\/aac.01054-06","article-title":"Phenotypic and genotypic characterization of Streptococcus pyogenes isolates displaying the MLSB phenotype of macrolide resistance in Spain, 1999 to 2005.","volume":"51","author":"P\u00e9rez-Trallero","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"B39","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s10096-011-1385-9","article-title":"Streptococcus pyogenes bacteraemia, emm types and superantigen profiles.","volume":"31","author":"Rantala","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1099\/jmm.0.46481-0","article-title":"Superantigen gene profile, emm type and antibiotic resistance genes among group A streptococcal isolates from Barcelona, Spain.","author":"Rivera","year":"2006","journal-title":"J. Med. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00542","article-title":"Identification and characterization of fluoroquinolone non-susceptible Streptococcus pyogenes clones harboring tetracycline and macrolide resistance in Shanghai, China.","volume":"9","author":"Shen","year":"2018","journal-title":"Front. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1586\/14787210.2015.1023292","article-title":"Macrolide-resistant Streptococcus pyogenes: prevalence and treatment strategies.","volume":"13","author":"Silva-Costa","year":"2015","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"35225","DOI":"10.1074\/jbc.M113.507673","article-title":"The prophage-encoded hyaluronate lyase has broad substrate specificity and is regulated by the N-terminal domain.","volume":"289","author":"Singh","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"7095","DOI":"10.1128\/iai.70.12.7095-7104.2002","article-title":"Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks.","volume":"70","author":"Smoot","year":"2002","journal-title":"Infect. Immun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/s1473-3099(09)70178-1","article-title":"Global emm type distribution of group A streptococci: systematic review and implications for vaccine development.","volume":"9","author":"Steer","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1007\/s10096-017-2978-8","article-title":"The virulence factors of group A streptococcus strains isolated from invasive and non-invasive infections in Polish and German centres, 2009\u20132011.","volume":"36","author":"Strus","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B47","year":"2021"},{"key":"B48","doi-asserted-by":"publisher","first-page":"S1684","DOI":"10.1016\/j.jmii.2020.08.019","article-title":"Emergence of macrolide-resistant Streptococcus pyogenes emm12 in southern Taiwan from 2000 to 2019.","author":"Tsai","year":"2020","journal-title":"J. Microbiol. Immunol. Infect. [Online ahead of print]"},{"key":"B49","doi-asserted-by":"publisher","first-page":"233","DOI":"10.5578\/mb.66841","article-title":"[Investigation of Streptococcus pyogenes virulence factors and typing by multiple locus variable number tandem repeat fingerprinting (MLVF) method].","volume":"52","author":"T\u00fcrk Da\u011f\u0131","year":"2018","journal-title":"Mikrobiyol. Bul."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002736","article-title":"DNase Sda1 allows invasive M1T1 Group A streptococcus to prevent TLR9-dependent recognition.","volume":"8","author":"Uchiyama","year":"2012","journal-title":"PLoS Pathog."},{"key":"B51","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1093\/cid\/ciz1000","article-title":"Streptococcus pyogenes pbp2x mutation confers reduced susceptibility to \u03b2-Lactam antibiotics.","volume":"71","author":"Vannice","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1089\/mdr.2013.0213","article-title":"Prevalence of macrolide resistance among group A streptococci isolated from pharyngotonsillitis.","volume":"20","author":"Wajima","year":"2014","journal-title":"Microb. Drug. Resist."},{"key":"B53","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1128\/cmr.00101-13","article-title":"Disease manifestations and pathogenic mechanisms of Group A Streptococcus.","volume":"27","author":"Walker","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.ebiom.2018.01.010","article-title":"Scarlet fever epidemic in China caused by streptococcus pyogenes serotype M12: epidemiologic and molecular analysis.","volume":"28","author":"You","year":"2018","journal-title":"EBioMedicine"},{"key":"B55","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/s1473-3099(19)30694-2","article-title":"8-year M type surveillance of Streptococcus pyogenes in China.","volume":"20","author":"You","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30441-2","article-title":"Changes in M types of Streptococcus pyogenes in Chinese children with scarlet fever.","volume":"20","author":"Yu","year":"2020","journal-title":"Lancet Infect. Dis."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.722225\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T16:07:03Z","timestamp":1639066023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.722225\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":56,"alternative-id":["10.3389\/fmicb.2021.722225"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.722225","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]},"article-number":"722225"}}