{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:21:23Z","timestamp":1792009283583,"version":"4.4.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R37AI051334"],"award-info":[{"award-number":["R37AI051334"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Treponema pallidum<\/jats:italic> subspecies <jats:italic>pallidum<\/jats:italic>, the causative agent of syphilis, traverses the vascular endothelium to gain access to underlying tissue sites. Herein, we investigate the mechanisms associated with <jats:italic>T. pallidum<\/jats:italic> traversal of endothelial barriers. Immunofluorescence microscopy reveals that a subpopulation of <jats:italic>T. pallidum<\/jats:italic> localizes to intercellular junctions and that viable <jats:italic>T. pallidum<\/jats:italic>, as well as a <jats:italic>T. pallidum<\/jats:italic> vascular adhesin (Tp0751), disrupts the architecture of the main endothelial junctional protein VE-cadherin. Intriguingly, in this study we show that <jats:italic>T. pallidum<\/jats:italic> traverses endothelial barriers with no disruption in barrier permeability. Furthermore, barrier traversal by <jats:italic>T. pallidum<\/jats:italic> is reduced by pretreatment of endothelial cells with filipin, an inhibitor that blocks cholesterol-mediated endocytosis. Collectively, these results suggest that <jats:italic>T. pallidum<\/jats:italic> can use a cholesterol-dependent, lipid raft-mediated endocytosis mechanism to traverse endothelial barriers. Further, treponemal localization to, and disruption of, intercellular junctions suggests that a paracellular route may also be utilized, a dual traversal strategy that has also been observed to occur for leukocytes and other invasive bacteria.<\/jats:p>","DOI":"10.3389\/fmicb.2021.691731","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T06:57:09Z","timestamp":1626764229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Treponema pallidum Disrupts VE-Cadherin Intercellular Junctions and Traverses Endothelial Barriers Using a Cholesterol-Dependent Mechanism"],"prefix":"10.3389","volume":"12","author":[{"given":"Karen V.","family":"Lithgow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Schovanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alloysius","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Anne","family":"Swayne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.4161\/cam.28243","article-title":"Dynamics between actin and the VE-cadherin\/catenin complex: novel aspects of the ARP2\/3 complex in regulation of endothelial junctions.","volume":"8","author":"Abu Taha","year":"2014","journal-title":"Cell Adh. 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