{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:50:22Z","timestamp":1791240622497,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Program 69","award":["40690_145211\/1"],"award-info":[{"award-number":["40690_145211\/1"]}]},{"name":"University of Zurich Forschungskredit","award":["FK-13-059"],"award-info":[{"award-number":["FK-13-059"]}]},{"name":"University of Zurich Forschungskredit","award":["FK-15-055"],"award-info":[{"award-number":["FK-15-055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences.<\/jats:p>","DOI":"10.3390\/toxins8060169","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T19:22:34Z","timestamp":1464808954000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-5651","authenticated-orcid":false,"given":"Sophia","family":"Johler","sequence":"first","affiliation":[{"name":"Institute for Food Safety and Hygiene, Vetsuisse Faculty University of Zurich, Winterthurerstrasse 272, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henna-Maria","family":"Sihto","sequence":"additional","affiliation":[{"name":"Institute for Food Safety and Hygiene, Vetsuisse Faculty University of Zurich, Winterthurerstrasse 272, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guerrino","family":"Macori","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Coagulase-Positive Staphylococci including <i>Staphylococcus aureus<\/i>, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d\u2019Aosta, Via Bologna 148, 10154 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1002-4762","authenticated-orcid":false,"given":"Roger","family":"Stephan","sequence":"additional","affiliation":[{"name":"Institute for Food Safety and Hygiene, Vetsuisse Faculty University of Zurich, Winterthurerstrasse 272, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3201\/eid1701.P11101","article-title":"Foodborne illness acquired in the United States\u2014Major pathogens","volume":"17","author":"Scallan","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/0140-6736(90)92500-H","article-title":"Foodborne staphylococcal illness","volume":"336","author":"Tranter","year":"1990","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.foodcont.2015.10.008","article-title":"Growth behavior and temporal enterotoxin D expression of Staphylococcus aureus strains under glucose and lactic acid stress","volume":"62","author":"Sihto","year":"2016","journal-title":"Food Control"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.foodcont.2016.01.007","article-title":"Effect of sodium nitrite and regulatory mutations \u0394agr, \u0394sarA, and \u0394sigB on the mRNA and protein levels of staphylococcal enterotoxin D","volume":"65","author":"Sihto","year":"2016","journal-title":"Food Control"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sihto, H.-M., Tasara, T., Stephan, R., and Johler, S. (2015). Temporal expression of the staphylococcal enterotoxin D gene under NaCl stress conditions encountered during food production and preservation. FEMS Microbiol. Lett., submitted for publication.","DOI":"10.1093\/femsle\/fnv024"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wallin-Carlquist, N., Cao, R., M\u00e1rta, D., da Silva, A.S., Schelin, J., and R\u00e5dstr\u00f6m, P. (2010). Acetic acid increases the phage-encoded enterotoxin A expression in Staphylococcus aureus. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-147"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1128\/AEM.00803-12","article-title":"Elevated enterotoxin A expression and formation in Staphylococcus aureus and its association with prophage Induction","volume":"78","author":"Cao","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.1128\/JB.185.23.6841-6851.2003","article-title":"Transcription of the toxin genes present within the staphylococcal phage \u03c6Sa3ms is intimately linked with the phage\u2019s life cycle","volume":"185","author":"Sumby","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1128\/iai.62.1.113-118.1994","article-title":"Phage-associated differences in staphylococcal enterotoxin A gene (sea) expression correlate with sea allele class","volume":"62","author":"Borst","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_10","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","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1128\/JB.182.8.2321-2325.2000","article-title":"Characterization of the promoter elements for the staphylococcal enterotoxin D gene","volume":"182","author":"Zhang","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1128\/iai.20.1.273-278.1978","article-title":"Chromosomal locus for staphylococcal enterotoxin B","volume":"20","author":"Shafer","year":"1978","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/1348-0421.12007","article-title":"A novel comprehensive analysis method for Staphylococcus aureus pathogenicity islands","volume":"57","author":"Omoe","year":"2013","journal-title":"Microbiol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Stevens, M.J.A., Stephan, R., and Johler, S. (2015). Complete and assembled genome sequence of Staphylococcus aureus RKI4, a food-poisoning strain exhibiting a novel S. aureus pathogenicity island carrying seb. Genome Announc., 3.","DOI":"10.1128\/genomeA.00769-15"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kohler, P.L., Greenwood, S.D., Nookala, S., Kotb, M., Kranz, D.M., and Schlievert, P.M. (2012). Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041157"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1128\/jb.171.8.4507-4510.1989","article-title":"Nucleotide sequence of the type C3 staphylococcal enterotoxin gene suggests that intergenic recombination causes antigenic variation","volume":"171","author":"Couch","year":"1989","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1128\/iai.61.10.4254-4262.1993","article-title":"Characterization of novel type C staphylococcal enterotoxins: biological and evolutionary implications","volume":"61","author":"Marr","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00329830","article-title":"Nucleotide sequence of the staphylococcal enterotoxin C1 gene and relatedness to other pyrogenic toxins","volume":"209","author":"Bohach","year":"1987","journal-title":"Mol. Gen. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1128\/JB.183.1.63-70.2001","article-title":"Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens","volume":"183","author":"Fitzgerald","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1128\/jb.171.9.4799-4806.1989","article-title":"Genetic and molecular analyses of the gene encoding staphylococcal enterotoxin D","volume":"171","author":"Bayles","year":"1989","journal-title":"J. Bacteriol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.4315\/0362-028X-69.6.1448","article-title":"Staphylococcal enterotoxin D production by Staphylococcus aureus FRI 100","volume":"69","author":"Kauffman","year":"2006","journal-title":"J. Food Prot."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1292\/jvms.15-0028","article-title":"Detection of the staphylococcal enterotoxin D-like gene from staphylococcal food poisoning isolates over the last two decades in Tokyo","volume":"77","author":"Suzuki","year":"2015","journal-title":"J. Vet. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1128\/genomeA.00284-14","article-title":"Genome sequence of bacterial interference strain Staphylococcus aureus 502A","volume":"2","author":"Parker","year":"2014","journal-title":"Genome Announc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1089\/fpd.2012.1185","article-title":"Production of staphylococcal enterotoxin R by Staphylococcus aureus strains","volume":"9","author":"Lis","year":"2012","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1128\/jb.166.1.29-33.1986","article-title":"Nucleotide sequence of the enterotoxin B gene from Staphylococcus aureus","volume":"166","author":"Jones","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1128\/jb.170.9.4033-4039.1988","article-title":"Staphylococcal enterotoxin B gene is associated with a discrete genetic element","volume":"170","author":"Johns","year":"1988","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/CMR.13.1.16","article-title":"Exotoxins of Staphylococcus aureus","volume":"13","author":"Dinges","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1365-2958.1994.tb00481.x","article-title":"Investigation of the role of the disulphide bond in the activity and structure of staphylococcal enterotoxin C1","volume":"15","author":"Hovde","year":"1994","journal-title":"Mol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tobes, R., Manrique, M., Brozynska, M., Stephan, R., Pareja, E., and Johler, S. (2013). Noncontiguous finished genome sequence of Staphylococcus aureus KLT6, a staphylococcal enterotoxin B-positive strain involved in a food poisoning outbreak in Switzerland. Genome Announc., 1.","DOI":"10.1128\/genomeA.00214-13"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s10096-011-1330-y","article-title":"Comparison of Staphylococcus aureus isolates associated with food intoxication with isolates from human nasal carriers and human infections","volume":"31","author":"Wattinger","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.meatsci.2015.11.002","article-title":"Genotyping and DNA microarray based characterization of Staphylococcus aureus isolates from rabbit carcasses","volume":"112","author":"Merz","year":"2016","journal-title":"Meat Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.4315\/0362-028X.JFP-11-192","article-title":"Comparison of virulence and antibiotic resistance genes of food poisoning outbreak isolates of Staphylococcus aureus with isolates obtained from bovine mastitis milk and pig carcasses","volume":"74","author":"Johler","year":"2011","journal-title":"J. Food Prot."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/8\/6\/169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:24:48Z","timestamp":1760210688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/8\/6\/169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,1]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["toxins8060169"],"URL":"https:\/\/doi.org\/10.3390\/toxins8060169","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,1]]}}}