{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:39:02Z","timestamp":1791527942471,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013939","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000}}],"reference-count":115,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI168148"],"award-info":[{"award-number":["P01 AI168148"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI167241"],"award-info":[{"award-number":["R21 AI167241"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI168148"],"award-info":[{"award-number":["P01 AI168148"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical College of Wisconsin Center for Immunology","award":["Pilot Grant"],"award-info":[{"award-number":["Pilot Grant"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Leptospirosis is a global zoonotic disease caused by pathogenic species of the genus\n                    <jats:italic>Leptospira<\/jats:italic>\n                    .\n                    <jats:italic>Leptospira<\/jats:italic>\n                    species are classified into two major clades (pathogenic, P, and saprophytic, S), and four subclades (P1, P2, S1, and S2), with the P1 subclade further divided into high virulence (P1+) and low virulence (P1-) groups. While previous studies have associated P1\u2009+\u2009species to greater virulence in the host, phenotypic characterization across clades, particularly regarding dissemination and cell barrier disruption, remains limited. In this study, sixteen strains of pathogenic and saprophytic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    representing subclades P1\u2009+\u2009, P1-, P2, and S1 were evaluated\n                    <jats:italic>in vitro<\/jats:italic>\n                    to assess association with human endothelial cells, disruption of host VE-cadherin localization in adherens junctions, and immune response as measured by cytokine and chemokine release. Our findings indicate that VE-cadherin disruption correlates with P1\u2009+\u2009species and the presence of virulence-associated genes. Additionally, bacterial association with host cells correlates with the loss of VE-cadherin localization in adherens junctions.\n                    <jats:italic>In vitro Leptospira<\/jats:italic>\n                    interaction with endothelial cells induced production of chemokine and cytokines, most prominent in the P1\u2009+\u2009clade and correlating with the presence of virulence-associated genes. Using an\n                    <jats:italic>in vivo<\/jats:italic>\n                    murine model of hematogenous dissemination to assess tissue tropism, live\n                    <jats:italic>Leptospira<\/jats:italic>\n                    were cultured from relevant tissues of animals inoculated with most of the strains tested and bacterial burdens were quantified to measure adhesion to tissues. Four of the six P1\u2009+\u2009strains exhibited significantly higher tissue burdens in kidney, liver, and bladder at one hour post-inoculation compared to other\n                    <jats:italic>Leptospira<\/jats:italic>\n                    species. Together, these results suggest that endothelial cell interactions may be a key phenotypic marker for virulence classification in\n                    <jats:italic>Leptospira<\/jats:italic>\n                    . Further defining these interactions may therefore provide insights into interventions to combat this potentially fatal disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013939","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:48:20Z","timestamp":1769539700000},"page":"e0013939","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["In vitro and in vivo endothelial interactions of Leptospira species are markers of virulence"],"prefix":"10.1371","volume":"20","author":[{"given":"Phillip N.","family":"Anderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth L.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger","family":"Thao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly Sue","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Giraud-Gatineau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4925-2059","authenticated-orcid":true,"given":"Matthew C.","family":"Surdel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"issue":"9","key":"pntd.0013939.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global Morbidity and Mortality of Leptospirosis: A Systematic Review","volume":"9","author":"F Costa","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0013939.ref002","article-title":"Leptospira.","volume-title":"Medical Microbiology","author":"RC. 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