{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:27:33Z","timestamp":1790616453978,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100007018","name":"Kimberly-Clark Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Toxic shock syndrome toxin 1 (TSST-1) is a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            superantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. The\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            exotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            , although regulation of TSST-1 by the Sae system has not been investigated. We generated a defined deletion mutant of the Sae histidine kinase sensor (\n            <jats:italic>saeS<\/jats:italic>\n            ) in the prototypic menstrual TSS strain\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            MN8. Mutation of\n            <jats:italic>saeS<\/jats:italic>\n            resulted in a complete loss of TSST-1 expression. Using both luciferase reporter experiments and quantitative real-time PCR, we demonstrate that the Sae system is an important transcriptional activator of TSST-1 expression. Recombinant SaeR was able to bind directly to the\n            <jats:italic>tst<\/jats:italic>\n            promoter to a region containing two SaeR consensus binding sites. Although the stand-alone SarA transcriptional regulator has been shown to be both a positive and a negative regulator of TSST-1, deletion of\n            <jats:italic>sarA<\/jats:italic>\n            in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            MN8 resulted in a dramatic overexpression of TSST-1. As expected, mutation of\n            <jats:italic>agr<\/jats:italic>\n            also reduced TSST-1 expression, but this phenotype appeared to be independent of Sae. A double mutation of\n            <jats:italic>saeS<\/jats:italic>\n            and\n            <jats:italic>sarA<\/jats:italic>\n            resulted in the loss of TSST-1 expression. This work indicates that the Sae system is a dominant and direct transcriptional activator that is required for expression of TSST-1.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The TSST-1 superantigen is an exotoxin, produced by some strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            , that has a clear role in both menstrual and nonmenstrual TSS. Although the well-characterized\n            <jats:italic>agr<\/jats:italic>\n            quorum sensing system is a known positive regulator of TSST-1, the molecular mechanisms that directly control TSST-1 expression are only partially understood. Our studies demonstrate that the Sae two-component regulatory system is a positive transcriptional regulator that binds directly to the TSST-1 promoter, and furthermore, our data suggest that Sae is required for expression of TSST-1. This work highlights how major regulatory circuits can converge to fine-tune exotoxin expression and suggests that the Sae regulatory system may be an important target for antivirulence strategies.\n          <\/jats:p>","DOI":"10.1128\/jb.00425-16","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:33:31Z","timestamp":1469500411000},"page":"2732-2742","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["The SaeRS Two-Component System Is a Direct and Dominant Transcriptional Activator of Toxic Shock Syndrome Toxin 1 in Staphylococcus aureus"],"prefix":"10.1128","volume":"198","author":[{"given":"Miren L.","family":"Baroja","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Herfst","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Kasper","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey X.","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Gillett","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Li","sequence":"additional","affiliation":[{"name":"Corporate Research &amp; Engineering, Kimberly-Clark Corporation, Roswell, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"},{"name":"Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.1.16-34.2000"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.55.1.77"},{"key":"e_1_3_2_5_2","volume-title":"Toxic shock syndrome; 2011 case definition","author":"Centers for Disease Control and Prevention","year":"2011","unstructured":"Centers for Disease Control and Prevention. 2011. Toxic shock syndrome; 2011 case definition. Centers for Disease Control and Prevention, Atlanta, GA."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022997"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198012183032501"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198012183032502"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00104-12"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S0140-6736(86)91859-3","article-title":"Staphylococcal enterotoxin B and toxic-shock syndrome toxin-1 are significantly associated with non-menstrual TSS","author":"Schlievert PM","year":"1986","unstructured":"Schlievert PM. 1986. Staphylococcal enterotoxin B and toxic-shock syndrome toxin-1 are significantly associated with non-menstrual TSS. Lancet i:1149\u20131150. (Letter.)","journal-title":"Lancet"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00330517"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.4.1113-1123.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-52"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00146-10"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.23.6232-6241.1998"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135579"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00724-08"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/147.2.236"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017431108"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(67)90105-5"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00308-15"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.11.6887-6891.2004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2005.05.005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.12.7851-7857.2001"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2009.01.003"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01524-09"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.189068"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004799"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.696625"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/649570"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja3112115"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05436-11"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00555-06"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.6.1843-1852.2001"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.13.4085-4099.2004"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111084108"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002030050469"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05292.x"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.423507"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06771-11"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00706-12"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01242-12"},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/1615-9861(200104)1:4<480::AID-PROT480>3.0.CO;2-O","article-title":"Extracellular proteins of Staphylococcus aureus and the role of SarA and sigma B","volume":"1","author":"Ziebandt AK","year":"2001","unstructured":"Ziebandt AK, Weber H, Rudolph J, Schmid R, H\u00f6per D, Engelmann S, Hecker M. 2001. Extracellular proteins of Staphylococcus aureus and the role of SarA and sigma B. Proteomics 1:480\u2013493.","journal-title":"Proteomics"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00383-08"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.02044-14"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2011.01.003"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1016\/S0021-9258(19)39612-7","article-title":"Role of upstream sequences in the expression of the staphylococcal enterotoxin B gene","volume":"265","author":"Mahmood R","year":"1990","unstructured":"Mahmood R, Khan SA. 1990. Role of upstream sequences in the expression of the staphylococcal enterotoxin B gene. J Biol Chem 265:4652\u20134656.","journal-title":"J Biol Chem"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.184.4.1095-1101.2002"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00425-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00425-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:40:56Z","timestamp":1627580456000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.00425-16"}},"subtitle":[],"editor":[{"given":"A. M.","family":"Stock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":47,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/JB.00425-16"],"URL":"https:\/\/doi.org\/10.1128\/jb.00425-16","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}