{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:37:23Z","timestamp":1782286643525,"version":"3.54.5"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100015158","name":"Fondren Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015158","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in\n            <jats:named-content content-type=\"genus-species\">Streptococcus pyogenes<\/jats:named-content>\n            . The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the\n            <jats:italic>rocA<\/jats:italic>\n            gene encoding a sensor kinase.\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the\n            <jats:italic>rocA<\/jats:italic>\n            gene. In summary, we identified and characterized an intergenic VNTR polymorphism in\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            that affects toxin production and virulence. These new findings enhance understanding of\n            <jats:italic>rocA<\/jats:italic>\n            biology and the function of VNTR polymorphisms in\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/iai.00258-16","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T01:59:30Z","timestamp":1462240770000},"page":"2086-2093","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of\n            <i>rocA<\/i>\n            Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes"],"prefix":"10.1128","volume":"84","author":[{"given":"Luchang","family":"Zhu","sequence":"first","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research 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