{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:51:30Z","timestamp":1773312690841,"version":"3.50.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T00:00:00Z","timestamp":1465948800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2016,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The genome of an invasive skin-tropic strain (AP53) of serotype M53 group A\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pyogenes<\/jats:named-content>\n            (GAS) is composed of a circular chromosome of 1,860,554 bp and carries genetic markers for infection at skin locales,\n            <jats:italic>viz<\/jats:italic>\n            .,\n            <jats:italic>emm<\/jats:italic>\n            gene family pattern D and FCT type 3. Through genome-scale comparisons of AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal a potential genetic basis for skin tropism. The genome of AP53 differed by \u223c30 point mutations from a noninvasive pattern D serotype M53 strain (Alab49), 4 of which are located in virulence genes. One pseudogene, yielding an inactive sensor kinase (CovS\n            <jats:sup>\u2212<\/jats:sup>\n            ) of the two-component transcriptional regulator CovRS, a major determinant for invasiveness, severely attenuated the expression of the secreted cysteine protease SpeB and enhanced the expression of the hyaluronic acid capsule compared to the isogenic noninvasive AP53\/CovS\n            <jats:sup>+<\/jats:sup>\n            strain. The collagen-binding protein transcript\n            <jats:italic>sclB<\/jats:italic>\n            differed in the number of 5\u2032-pentanucleotide repeats in the signal peptides of AP53 and Alab49 (9 versus 15), translating into different lengths of their signal peptides, which nonetheless maintained a full-length translatable coding frame. Furthermore, GAS strain AP53 acquired two phages that are absent in Alab49. One such phage (\u03a6AP53.2) contains the known virulence factor superantigen exotoxin gene tandem\n            <jats:italic>speK-slaA<\/jats:italic>\n            . Overall, we conclude that this bacterium has evolved in multiple ways, including mutational variations of regulatory genes, short-tandem-repeat polymorphisms, large-scale genomic alterations, and acquisition of phages, all of which may be involved in shaping the adaptation of GAS in specific infectious environments and contribute to its enhanced virulence.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Infectious strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pyogenes<\/jats:named-content>\n            (GAS) are classified by their serotypes, relating to the surface M protein, the\n            <jats:italic>emm<\/jats:italic>\n            -like subfamily pattern, and their tropicity toward the nasopharynx and\/or skin. It is generally agreed that M proteins from pattern D strains, which also directly bind human host plasminogen, are skin tropic. We have sequenced and characterized the genome of an invasive pattern D GAS strain (AP53) in comparison to a very similar strain (Alab49) that is noninvasive and developed a genomic rationale as to possible reasons for the skin tropicity of these two strains and the greater invasiveness of AP53.\n          <\/jats:p>","DOI":"10.1128\/jb.01019-15","type":"journal-article","created":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T03:18:36Z","timestamp":1459826316000},"page":"1712-1724","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Genomic Characterization of a Pattern D Streptococcus pyogenes\n            <i>emm53<\/i>\n            Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity"],"prefix":"10.1128","volume":"198","author":[{"given":"Yun-Juan","family":"Bao","sequence":"first","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Liang","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"},{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Mayfield","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah L.","family":"Donahue","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelyn E.","family":"Carothers","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun W.","family":"Lee","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"},{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria A.","family":"Ploplis","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"},{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis J.","family":"Castellino","sequence":"additional","affiliation":[{"name":"W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA"},{"name":"Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"91","article-title":"The antigenic complex of Streptococcus haemolyticus. I","volume":"47","author":"Lancefield RC","year":"1928","unstructured":"Lancefield RC. 1928. The antigenic complex of Streptococcus haemolyticus. I. Demonstration of a type-specific substance in extracts of Streptococcus haemolyticus. 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