{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:30:56Z","timestamp":1791592256173,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> Necrotizing fasciitis (NF) caused by <jats:italic>S. aureus<\/jats:italic> is a rare, aggressive and rapidly progressing superficial fascia infection with a high mortality rate. The aim of this study was to identify virulence-related genes from a complete genome sequence of a methicillin-susceptible <jats:italic>S. aureus<\/jats:italic> (MSSA) isolate recovered from a monomicrobial case of NF.<\/jats:p><jats:p><jats:bold>Materials and methods:<\/jats:bold> The MSSA isolate UMCG579 was cultured from a pus collection from the subcutis of a patient with NF. The genome of isolate UMCG579 was sequenced using MinION (Oxford Nanopore) and MiSeq (illumina) platforms.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The genome of the UMCG579 isolate was composed of a 2,741,379\u00a0bp chromosome and did not harbor any plasmids. Virulence factor profiling identified multiple pore-forming toxin genes in the UMCG579 chromosome, including the Panton-Valentine leukocidin (PVL) genes, and none of the superantigen genes. The UMCG579 isolate harbored a new sequence variant of the recently described <jats:italic>ete<\/jats:italic> gene encoding exfoliative toxin (type E). A search in the GenBank database revealed that the new sequence variant (<jats:italic>ete2<\/jats:italic>) was exclusively found among isolates (<jats:italic>n<\/jats:italic> = 115) belonging to MLST CC152. While the majority of <jats:italic>S. aureus ete<\/jats:italic>-positive isolates were recovered from animal sources, <jats:italic>S. aureus ete2<\/jats:italic>-positive isolates originated from human carriers and human infections. Comparative genome analysis revealed that the <jats:italic>ete2<\/jats:italic> gene was located on a 8777 bp genomic island.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The combination of two heterogeneously distributed potent toxins, ETE2 and PVL, is likely to enhance the pathogenic ability of <jats:italic>S. aureus<\/jats:italic> isolates. Since anti-virulence therapies for the treatment of <jats:italic>S. aureus<\/jats:italic> infections continue to be explored, the understanding of specific pathogenetic mechanisms may have an important prophylactic and therapeutic value. Nevertheless, the exact contribution of ETE sequence variants to <jats:italic>S. aureus<\/jats:italic> virulence in NF infections must be determined.<\/jats:p>","DOI":"10.3389\/fgene.2022.964358","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T09:10:44Z","timestamp":1663233044000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Case Report: Necrotizing fasciitis caused by Staphylococcus aureus positive for a new sequence variant of exfoliative toxin E"],"prefix":"10.3389","volume":"13","author":[{"given":"Artur J.","family":"Sabat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Wouthuyzen-Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique","family":"Rondags","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Akkerboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Koutsopetra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W.","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Bathoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/81385","article-title":"Toxin in bullous impetigo and staphylococcal scalded-skin syndrome targets desmoglein 1","volume":"6","author":"Amagai","year":"2000","journal-title":"Nat. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1046\/j.1523-1747.2002.01751.x","article-title":"Staphylococcal exfoliative toxin B specifically cleaves desmoglein 1","volume":"118","author":"Amagai","year":"2002","journal-title":"J. Invest. Dermatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"W16","DOI":"10.1093\/nar\/gkw387","article-title":"PHASTER: a better, faster version of the PHAST phage search tool","volume":"44","author":"Arndt","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12864-018-5394-2","article-title":"Virulence factor landscape of a Staphylococcus aureus sequence type 45 strain, MCRF184","volume":"20","author":"Aswani","year":"2019","journal-title":"BMC Genomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"663831","DOI":"10.3389\/fmicb.2021.663831","article-title":"Genomic epidemiology and global population structure of exfoliative toxin A-producing Staphylococcus aureus strains associated with staphylococcal scalded skin syndrome","volume":"12","author":"Azarian","year":"2021","journal-title":"Front. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.jgar.2018.05.006","article-title":"Genomic insights of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) with reduced teicoplanin susceptibility: a case of fatal necrotizing fasciitis","volume":"14","author":"Bakthavatchalam","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4305","DOI":"10.1128\/jcm.01979-14","article-title":"Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus","volume":"52","author":"Bartels","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"W30","DOI":"10.1093\/nar\/gkx343","article-title":"IslandViewer 4: expanded prediction of genomic islands for larger-scale datasets","volume":"45","author":"Bertelli","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.3390\/toxins2051148","article-title":"Exfoliative toxins of Staphylococcus aureus","volume":"2","author":"Bukowski","year":"2010","journal-title":"Toxins (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1007\/s00134-016-4576-0","article-title":"Diagnosis and management of skin and soft tissue infections in the intensive care unit: a review","volume":"42","author":"Burnham","year":"2016","journal-title":"Intensive Care Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000247443","article-title":"Staphylococcus aureus leukocidin: a new virulence factor in cutaneous infections? An epidemiological and experimental study","volume":"185","author":"Cribier","year":"1992","journal-title":"Dermatology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1086\/519263","article-title":"Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin","volume":"45","author":"Gillet","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1086\/591803","article-title":"Association of necrotizing pneumonia with Panton-Valentine leukocidin-producing Staphylococcus aureus, regardless of methicillin resistance","volume":"47","author":"Gillet","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e119","DOI":"10.1002\/bjs.9371","article-title":"Early diagnosis of necrotizing fasciitis","volume":"101","author":"Goh","year":"2014","journal-title":"Br. J. Surg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.meegid.2013.03.013","article-title":"Staphylococcus aureus toxins--their functions and genetics","volume":"21","author":"Grumann","year":"2014","journal-title":"Infect. Genet. Evol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5268","DOI":"10.1074\/jbc.M311087200","article-title":"Enzymatic and molecular characteristics of the efficiency and specificity of exfoliative toxin cleavage of desmoglein 1","volume":"279","author":"Hanakawa","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1128\/jcm.43.5.2384-2390.2005","article-title":"Staphylococcus aureus isolates carrying panton-valentine leucocidin genes in england and wales: frequency, characterization, and association with clinical disease","volume":"43","author":"Holmes","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"16336","DOI":"10.1038\/s41598-019-52777-3","article-title":"Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity","volume":"9","author":"Imanishi","year":"2019","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e104984","DOI":"10.1371\/journal.pone.0104984","article-title":"Solving the problem of comparing whole bacterial genomes across different sequencing platforms","volume":"9","author":"Kaas","year":"2014","journal-title":"PLoS One"},{"key":"B20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.amjsurg.2010.07.041","article-title":"Local variations in the epidemiology, microbiology, and outcome of necrotizing soft-tissue infections: a multicenter study","volume":"202","author":"Kao","year":"2011","journal-title":"Am. J. Surg."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1097\/corr.0000000000001187","article-title":"What demographic and clinical factors are associated with in-hospital mortality in patients with necrotizing fasciitis?","volume":"478","author":"Karnuta","year":"2020","journal-title":"Clin. Orthop. Relat. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e00612","DOI":"10.1128\/mSphere.00612-17","article-title":"SCCmecFinder, a web-based tool for typing of staphylococcal cassette chromosome mec in Staphylococcus aureus using whole-genome sequence data","volume":"3","author":"Kaya","year":"2018","journal-title":"mSphere"},{"key":"B23","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4103\/jets.Jets_42_17","article-title":"Necrotizing fasciitis: how reliable are the cutaneous signs?","volume":"10","author":"Kiat","year":"2017","journal-title":"J. Emerg. Trauma Shock"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0218668","DOI":"10.1371\/journal.pone.0218668","article-title":"Etiology, characteristics, and outcomes of community-onset necrotizing fasciitis in korea: A multicenter study","volume":"14","author":"Kim","year":"2019","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1093\/infdis\/jir441","article-title":"Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection","volume":"204","author":"Kobayashi","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1128\/jcm.06094-11","article-title":"Multilocus sequence typing of total-genome-sequenced bacteria","volume":"50","author":"Larsen","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"5883","DOI":"10.1073\/pnas.0900743106","article-title":"Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus","volume":"106","author":"Li","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e22864","DOI":"10.1371\/journal.pone.0022864","article-title":"Panton-Valentine leukocidin does play a role in the early stage of Staphylococcus aureus skin infections: a rabbit model","volume":"6","author":"Lipinska","year":"2011","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e1000715","DOI":"10.1371\/journal.ppat.1000715","article-title":"Staphylococcus aureus panton-valentine leukocidin is a very potent cytotoxic factor for human neutrophils","volume":"6","author":"L\u00f6ffler","year":"2010","journal-title":"PLoS Pathog."},{"key":"B30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jdermsci.2007.05.007","article-title":"Staphylococcal exfoliative toxins: \"molecular scissors\" of bacteria that attack the cutaneous defense barrier in mammals","volume":"49","author":"Nishifuji","year":"2008","journal-title":"J. Dermatol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.cmi.2015.01.016","article-title":"Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe","volume":"21","author":"Nurjadi","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"B32","doi-asserted-by":"publisher","first-page":"E912","DOI":"10.3390\/microorganisms8060912","article-title":"Molecular characterization and pathogenicity of Staphylococcus aureus isolated from Benin-city, Nigeria","volume":"8","author":"Obasuyi","year":"2020","journal-title":"Microorganisms"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1017\/s0950268813003117","article-title":"Population dynamics of Staphylococcus aureus from northeastern Nigeria in 2007 and 2012","volume":"142","author":"Okon","year":"2014","journal-title":"Epidemiol. Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"E252","DOI":"10.3390\/toxins10060252","article-title":"Staphylococcus aureus toxins and their molecular activity in infectious diseases","volume":"10","author":"Oliveira","year":"2018","journal-title":"Toxins (Basel)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1111\/1469-0691.12690","article-title":"New epidemiology of Staphylococcus aureus infection in Africa","volume":"20","author":"Schaumburg","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"B36","doi-asserted-by":"publisher","first-page":"E332","DOI":"10.3390\/toxins11060332","article-title":"The role of streptococcal and staphylococcal exotoxins and proteases in human necrotizing soft tissue infections","volume":"11","author":"Shumba","year":"2019","journal-title":"Toxins (Basel)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1056\/NEJMra1600673","article-title":"Necrotizing soft-tissue infections","volume":"377","author":"Stevens","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.idc.2020.10.004","article-title":"Necrotizing soft tissue infections","volume":"35","author":"Stevens","year":"2021","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1128\/aac.01147-12","article-title":"A new local variant (ST764) of the globally disseminated ST5 lineage of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) carrying the virulence determinants of community-associated MRSA","volume":"57","author":"Takano","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular evolutionary genetics analysis version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.jiph.2015.06.003","article-title":"Epidemiology of necrotizing infection caused by Staphylococcus aureus and Streptococcus pyogenes at an Iowa hospital","volume":"8","author":"Thapaliya","year":"2015","journal-title":"J. Infect. Public Health"},{"key":"B42","doi-asserted-by":"publisher","first-page":"800970","DOI":"10.3389\/fphar.2022.800970","article-title":"Three-dimensional structure characterization and inhibition study of exfoliative toxin D from Staphylococcus aureus","volume":"13","author":"Ullah","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"978","DOI":"10.3201\/eid0908.030089","article-title":"Community-acquired methicillin-resistant Staphylococcus aureus carrying panton-valentine leukocidin genes: worldwide emergence","volume":"9","author":"Vandenesch","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e02082","DOI":"10.1128\/mBio.02082-20","article-title":"Population analysis of Staphylococcus aureus reveals a cryptic, highly prevalent superantigen SElW that contributes to the pathogenesis of bacteremia","volume":"11","author":"Vrieling","year":"2020","journal-title":"mBio"},{"key":"B45","doi-asserted-by":"publisher","first-page":"E2052","DOI":"10.3390\/microorganisms8122052","article-title":"Molecular characterization of Staphylococcus aureus isolated from chronic infected wounds in rural Ghana","volume":"8","author":"Wolters","year":"2020","journal-title":"Microorganisms"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.2169\/internalmedicine.4334-19","article-title":"Monomicrobial fournier's gangrene caused by panton-valentine leukocidin-negative methicillin-susceptible Staphylococcus aureus ST8 in Japan","volume":"59","author":"Yamagishi","year":"2020","journal-title":"Intern. Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.964358\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T09:10:48Z","timestamp":1663233048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.964358\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":46,"alternative-id":["10.3389\/fgene.2022.964358"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.964358","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]},"article-number":"964358"}}