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In this study, we employed a large-scale screen, signature-tagged mutagenesis (STM), to identify\n            <jats:italic>Streptococcus pyogenes<\/jats:italic>\n            virulence genes important for pathogenesis within the host. Approximately 1,200 STM mutants were created and screened using the zebrafish infectious disease model. The transposon insertion site was identified for 29 of the 150 mutants that were considered attenuated for virulence. Previously reported streptococcal virulence genes, such as\n            <jats:italic>mga<\/jats:italic>\n            ,\n            <jats:italic>hasA<\/jats:italic>\n            ,\n            <jats:italic>amrA<\/jats:italic>\n            ,\n            <jats:italic>smeZ<\/jats:italic>\n            , and two genes in the\n            <jats:italic>sil<\/jats:italic>\n            locus, were identified, confirming the utility of the model for revealing genes important for virulence. Multiple genes not previously implicated in virulence were also identified, including genes encoding putative transporters, hypothetical cytosolic proteins, and macrolide efflux pumps. The STM mutant strains display various levels of attenuation, and multiple separate insertions were identified in either the same gene or the same locus, suggesting that these factors are important for this type of acute, invasive infection. We further examined two such genes,\n            <jats:italic>silB<\/jats:italic>\n            and\n            <jats:italic>silC<\/jats:italic>\n            of a putative quorum-sensing regulon, and determined that they are significant virulence factors in our model of necrotizing fasciitis.\n            <jats:italic>sil<\/jats:italic>\n            locus promoter expression was examined under various in vitro conditions, as well as in zebrafish tissues, and was found to be differentially induced. This study was a unique investigation of\n            <jats:italic>S. pyogenes<\/jats:italic>\n            factors required for successful invasive infection.\n          <\/jats:p>","DOI":"10.1128\/iai.01306-08","type":"journal-article","created":{"date-parts":[[2009,2,18]],"date-time":"2009-02-18T03:34:52Z","timestamp":1234928092000},"page":"1854-1865","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["First\n            <i>Streptococcus pyogenes<\/i>\n            Signature-Tagged Mutagenesis Screen Identifies Novel Virulence Determinants"],"prefix":"10.1128","volume":"77","author":[{"given":"Anne E.","family":"Kizy","sequence":"first","affiliation":[{"name":"Immunology and Microbiology Department, Wayne State University School of Medicine, 540 E. 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