{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:40:50Z","timestamp":1790419250778,"version":"4.1.0"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"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":["Infect Immun"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            To obtain new information about\n            <jats:named-content content-type=\"genus-species\">Streptococcus pyogenes<\/jats:named-content>\n            intrahost genetic variation during invasive infection, we sequenced the genomes of 2,954 serotype M1 strains recovered from a nonhuman primate experimental model of necrotizing fasciitis. A total of 644 strains (21.8%) acquired polymorphisms relative to the input parental strain. The\n            <jats:italic>fabT<\/jats:italic>\n            gene, encoding a transcriptional regulator of fatty acid biosynthesis genes, contained 54.5% of these changes. The great majority of polymorphisms were predicted to deleteriously alter FabT function. Transcriptome-sequencing (RNA-seq) analysis of a wild-type strain and an isogenic\n            <jats:italic>fabT<\/jats:italic>\n            deletion mutant strain found that between 3.7 and 28.5% of the\n            <jats:named-content content-type=\"genus-species\">S. pyogenes<\/jats:named-content>\n            transcripts were differentially expressed, depending on the growth temperature (35\u00b0C or 40\u00b0C) and growth phase (mid-exponential or stationary phase). Genes implicated in fatty acid synthesis and lipid metabolism were significantly upregulated in the\n            <jats:italic>fabT<\/jats:italic>\n            deletion mutant strain. FabT also directly or indirectly regulated central carbon metabolism genes, including pyruvate hub enzymes and fermentation pathways and virulence genes. Deletion of\n            <jats:italic>fabT<\/jats:italic>\n            decreased virulence in a nonhuman primate model of necrotizing fasciitis. In addition, the\n            <jats:italic>fabT<\/jats:italic>\n            deletion strain had significantly decreased survival in human whole blood and during phagocytic interaction with polymorphonuclear leukocytes\n            <jats:italic>ex vivo<\/jats:italic>\n            . We conclude that FabT mutant progeny arise during infection, constitute a metabolically distinct subpopulation, and are less virulent in the experimental models used here.\n          <\/jats:p>","DOI":"10.1128\/iai.00608-16","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T01:30:00Z","timestamp":1473211800000},"page":"3268-3281","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Genomic Landscape of Intrahost Variation in Group A Streptococcus: Repeated and Abundant Mutational Inactivation of the\n            <i>fabT<\/i>\n            Gene Encoding a Regulator of Fatty Acid Synthesis"],"prefix":"10.1128","volume":"84","author":[{"given":"Jesus M.","family":"Eraso","sequence":"first","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and 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, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Beres","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Kachroo","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline R.","family":"Porter","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Nasser","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Texas A&amp;M Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"DeLeo","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Musser","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.3.470-511.2000"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38095"},{"key":"e_1_3_3_4_2","first-page":"329","article-title":"Pathogenesis of group A streptococcal infections","volume":"13","author":"Henningham A","year":"2012","unstructured":"Henningham A, Barnett TC, Maamary PG, Walker MJ. 2012. Pathogenesis of group A streptococcal infections. Discov Med 13:329\u2013342.","journal-title":"Discov Med"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/521263"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.03.002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01788-14"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510279103"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45169"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00405-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.03023-14"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00403-16"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403138111"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82478"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911811107"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.12.037"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts690"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02164-14"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308638200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)48640-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1159\/000360478"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.092148299"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2010.10.004"},{"key":"e_1_3_3_25_2","first-page":"255","article-title":"A non-human primate model of acute group a Streptococcus pharyngitis","volume":"431","author":"Sumby P","year":"2008","unstructured":"Sumby P, Tart AH, Musser JM. 2008. A non-human primate model of acute group a Streptococcus pharyngitis. Methods Mol Biol 431:255\u2013267.","journal-title":"Methods Mol Biol"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102135"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.10.018"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020005"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1086\/520147"},{"key":"e_1_3_3_30_2","first-page":"51","article-title":"Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins","volume":"8","author":"Wilkinson SP","year":"2006","unstructured":"Wilkinson SP, Grove A. 2006. Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins. Curr Issues Mol Biol 8:51\u201362.","journal-title":"Curr Issues Mol Biol"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-6712.2002.00069.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.02043-12"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12076"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04951.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601393"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01393-12"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400485200"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.6.2440-2449.1994"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.081851"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(96)00168-X"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040037"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00001-08"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.267674"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.15.4319-4327.2000"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.03.004"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.5.513"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319900111"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00688-09"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12005"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00155-06"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1304"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00278-15"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2015.02.010"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.04.002"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1839"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01596-14"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00440-09"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407460101"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00127-11"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/137.4.903"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1086\/367993"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01692-14"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520255113"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111084108"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1182395"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-237"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.9.4649-4653.2005"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2005.01338.x"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100698"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018249108"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00608-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00608-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:10:09Z","timestamp":1646475009000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00608-16"}},"subtitle":[],"editor":[{"given":"V. B.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":69,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1128\/IAI.00608-16"],"URL":"https:\/\/doi.org\/10.1128\/iai.00608-16","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"2016-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}