{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:32:15Z","timestamp":1791919935642,"version":"4.3.4"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"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":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Increased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. Although\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            alpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects 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            alpha-toxin on human epithelial barrier functions. We hypothesize that\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            alpha-toxin in the blood can impair the intestinal epithelial barrier and thereby facilitate the translocation of luminal bacteria into the blood, which may in turn aggravate a septic condition. Here, we showed that staphylococcal alpha-toxin disrupts the barrier integrity of human intestinal epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER) and reduced cellular levels of junctional proteins, such as ZO-1, ZO-3, and E-cadherin. The Caco-2 cells also responded to alpha-toxin with an elevated cytosolic calcium ion concentration ([Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>i<\/jats:sub>\n            ), elicited primarily by calcium influx from the extracellular environment, as well as with a significant reduction in TER, which was modulated by intracellular calcium chelation. Moreover, a significantly larger reduction in TER and amounts of the junctional proteins,\n            <jats:italic>viz<\/jats:italic>\n            ., ZO-3 and occludin, was achieved by basolateral than by apical application of the alpha-toxin. These experimental findings thus support the hypothesis that free staphylococcal alpha-toxin in the bloodstream may cause intestinal epithelial barrier dysfunction and further aggravate the septic condition by promoting the release of intestinal bacteria into the underlying tissues and the blood.\n          <\/jats:p>","DOI":"10.1128\/iai.00001-12","type":"journal-article","created":{"date-parts":[[2012,2,22]],"date-time":"2012-02-22T02:35:46Z","timestamp":1329878146000},"page":"1670-1680","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity"],"prefix":"10.1128","volume":"80","author":[{"given":"Young-Keun","family":"Kwak","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vikstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Eric","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"V\u00e9csey-Semj\u00e9n","sequence":"additional","affiliation":[{"name":"House of Science, Alba Nova University Centre, Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Colque-Navarro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"M\u00f6llby","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0602-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000191137.12774.b2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000045576.55937.67"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90349-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5458.1604"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2011.03.010"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.55.4.733-751.1991"},{"key":"e_1_3_2_9_2","first-page":"101","article-title":"Pathogenesis of sepsis syndrome: possible relevance of pore-forming bacterial toxins","volume":"216","author":"Bhakdi S","year":"1996","unstructured":"BhakdiS. 1996. 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