{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:27:41Z","timestamp":1781497661669,"version":"3.54.1"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"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":["mBio"],"published-print":{"date-parts":[[2015,10,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Strains of\n            <jats:italic>emm89<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">Streptococcus pyogenes<\/jats:named-content>\n            have become one of the major causes of invasive infections worldwide in the last 10\u00a0years. We recently sequenced the genome of 1,125\n            <jats:italic>emm89<\/jats:italic>\n            strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3\n            <jats:italic>nga<\/jats:italic>\n            promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the\n            <jats:italic>hasABC<\/jats:italic>\n            locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that\n            <jats:italic>emm89<\/jats:italic>\n            strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3\n            <jats:italic>emm89<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            (group A streptococcus [GAS]) causes pharyngitis (\u201cstrep throat\u201d), necrotizing fasciitis, and other human infections. Serious infections caused by\n            <jats:italic>emm89<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            strains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a new\n            <jats:italic>emm89<\/jats:italic>\n            clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO.\n            <jats:italic>emm89<\/jats:italic>\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            strains with the clade 3 phenotype (absence of capsule and high expression of SPN and SLO) are highly virulent in mice. These findings provide new understanding of how new virulent clones emerge and cause severe infections worldwide. This newfound knowledge of\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            virulence can be used to help understand future epidemics and conduct new translational research.\n          <\/jats:p>","DOI":"10.1128\/mbio.01378-15","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T01:11:02Z","timestamp":1444180262000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of\n            <i>emm89<\/i>\n            Streptococcus pyogenes"],"prefix":"10.1128","volume":"6","author":[{"given":"Luchang","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Nasser","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"de la Riva Morales","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey, Nuevo Le\u00f3n, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Musser","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470-511.2000"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70178-1"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2013.07.004"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071558"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.08.013"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.063412-0"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268814001265"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00622-15"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1711.110159"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/519936"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-12-280"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2010.00652.x"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00070-11"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02155-08"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1226-x"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/521264"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03624.x"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid\/1706.100804"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82478"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0010035"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506879200"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbaexp.2004.10.011"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003842"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000817"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.8.4786"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020005"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02035-14"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.19.8317"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.1.64-71.1997"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.5.1495-1501.1996"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00413-12"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003394"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01690-14"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07427.x"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1086\/432514"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911811107"},{"key":"e_1_3_1_38_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals","year":"2011","unstructured":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.","edition":"8"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403138111"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01378-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01378-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T01:59:12Z","timestamp":1646704752000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01378-15"}},"subtitle":[],"editor":[{"given":"Eric J.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,10,30]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,10,30]]}},"alternative-id":["10.1128\/mBio.01378-15"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01378-15","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,30]]},"assertion":[{"value":"2015-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01378-15"}}