{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:47Z","timestamp":1790315987208,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The commensal fungus\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      , a natural inhabitant of the human gut, can transition to a pathogenic state and disseminate into the blood. Disruption of the intestinal mucosal barrier, particularly through the impairment of epithelial cell integrity and intercellular junctions, is a critical step in this dissemination process. While candidalysin is a pore-forming cytolytic peptide encoded within ECE1 (extent of cell elongation 1 gene), its relationship to the abundance and organization of specific intestinal tight-junction proteins during dissemination remains incompletely defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology\/principal findings<\/jats:title>\n                    <jats:p>\n                      A murine model and human colonic epithelial cells (NCM-460) were used to investigate the effect of candidalysin on fungal dissemination and its association with changes in tight-junction protein abundance and distribution.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , infection with a candidalysin-deficient\n                      <jats:italic>C. albicans<\/jats:italic>\n                      mutant preserved TJ architecture, substantially reduced pro-inflammatory cytokine responses, and substantially reduced the frequency and amount of detectable fungal DNA in blood. In contrast, infection caused by wild-type (WT) and\n                      <jats:italic>ECE1<\/jats:italic>\n                      -reconstituted strains resulted in elevated serum levels of the pro-inflammatory cytokines IL-6, IL-1\u03b2, and TNF-\u03b1, accompanied by reduced protein expressions of the TJ components (ZO-1, Occludin, and Claudin-1).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , experiments using purified candidalysin demonstrated a biphasic, dose-dependent effect on TJ proteins. At 3.125 \u03bcg\/mL, TJ-associated signals were preserved and selected protein measurements were modestly increased, whereas transcript levels showed a slight reduction. At higher concentrations (\u226512.5 \u03bcg\/mL, up to 50 \u03bcg\/mL), higher candidalysin concentrations were associated with pronounced loss and discontinuity of TJ-associated signals and reduced abundance of selected TJ proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion\/significance<\/jats:title>\n                    <jats:p>The dose-dependent effects of candidalysin on epithelial junction-associated proteins support a context-dependent contribution to intestinal pathogenesis. These findings associate candidalysin with epithelial injury and dissemination in the present model but do not establish a binary molecular switch or a candidalysin-exclusive mechanism. Elucidating how candidalysin coordinates epithelial and immune pathways provides new insight into the mechanisms that sustain gut\u2013fungal symbiosis and may reveal therapeutic targets to preserve mucosal integrity and prevent systemic candidiasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1919478","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:44Z","timestamp":1790314304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tight junction suppression by candidalysin promotes gut-to-blood dissemination of Candida albicans"],"prefix":"10.3389","volume":"17","author":[{"given":"Yahui","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Dermatology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]},{"name":"Laboratory of Medical Mycology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]},{"name":"Medical Aesthetics Department\/Skin Health Management and Aesthetics Center, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Changzheng Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Georgetown University Medical Center","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]},{"name":"Laboratory of Medical Mycology, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]},{"name":"Medical Aesthetics Department\/Skin Health Management and Aesthetics Center, Jining No.1 People\u2019s Hospital, Jining","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e915","DOI":"10.1128\/mBio.00915-18","article-title":"Candida albicans-induced epithelial damage mediates translocation through intestinal.","volume":"9","author":"Allert","year":"2018","journal-title":"mBio"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1038\/s41467-022-30661-5","article-title":"Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity.","volume":"13","author":"Alonso-Roman","year":"2022","journal-title":"Nat. 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