{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:57:09Z","timestamp":1787021829197,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013693","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02281"],"award-info":[{"award-number":["24K02281"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100024224","name":"Chemo-Sero-Therapeutic Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Leptospirosis is a bacterial infection common in tropical and subtropical regions, which causes feverish conditions. Although approximately half of human leptospirosis cases in Japan are reported in Okinawa, a subtropical area, the pathogenic mechanisms of clinical isolates from this region remain unknown. This study aimed to identify the infection mechanisms of\n                      <jats:italic>\n                        <jats:italic>L. interrogans<\/jats:italic>\n                      <\/jats:italic>\n                      isolates from Okinawa (Oki-strains) in human renal proximal tubule epithelial cells (RPTECs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/principal findings<\/jats:title>\n                    <jats:p>The transepithelial electrical resistance (TEER) measurements of 11 Oki-strains in infected renal proximal tubule epithelial cells (RPTECs) showed that all strains caused a decrease in TEER by 48 hours post-infection. Imaging analysis of RPTECs infected with two selected strains (Oki53 and Oki65) revealed that both strains induced the displacement of adherens junction (AJ) proteins E-cadherin, \u03b1-catenin, afadin, and nectin-2 and cytoskeletal F-actin disorganization. However, western blotting analysis revealed that AJ protein levels were not reduced, except for afadin\u2014an important protein for linking F-actin to AJs. Chemical inhibition revealed that the proteosome inhibitors MG132 and bortezomib and pan-caspase inhibitor Z-VAD-FMK prevented the Oki53-induced TEER decrease, AJ protein mislocalization, afadin degradation, and F-actin disorganization. However, in Oki65-infected RPTECs, the inhibitors partially prevented these effects. Thus, the AJ-F-actin link and epithelial barrier were fully preserved in Oki53-infected RPTECs pretreated with these inhibitors at 24\u2009h post-infection (~TEER 130% of initial TEER), whereas in Oki65-infected cells, the AJ-F-actin link was maintained only partially (~TEER 70%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/significance<\/jats:title>\n                    <jats:p>Our findings suggest that the maintenance of epithelial barrier integrity requires both the afadin-F-actin and \u03b1-catenin-F-actin links, and that Oki53 and Oki65 employ distinct strategies to disrupt the AJ-F-actin link and, thus, the epithelial barrier.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013693","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:38:42Z","timestamp":1762281522000},"page":"e0013693","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distinct strategies of epithelial cell barrier disruption by Leptospira interrogans isolated from human patients in Okinawa, Japan"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-7397","authenticated-orcid":true,"given":"Tetsuya","family":"Kakita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-1722","authenticated-orcid":true,"given":"Claudia","family":"Toma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Sebasti\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Barbee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Yamashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"issue":"9","key":"pntd.0013693.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"},{"issue":"10","key":"pntd.0013693.ref002","article-title":"Leptospira sanjuanensis sp. nov., a pathogenic species of the genus Leptospira isolated from soil in Puerto Rico","volume":"72","author":"LGV Fernandes","year":"2022","journal-title":"Int J Syst Evol Microbiol"},{"issue":"5","key":"pntd.0013693.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007270","article-title":"Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics","volume":"13","author":"AT Vincent","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"11","key":"pntd.0013693.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011733","article-title":"Phylogenomics of Leptospira santarosai, a prevalent pathogenic species in the Americas","volume":"17","author":"D Chinchilla","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"pntd.0013693.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012161","article-title":"Evolutionary insights into the emergence of virulent Leptospira spirochetes","volume":"20","author":"A Giraud-Gatineau","year":"2024","journal-title":"PLoS Pathog"},{"issue":"2","key":"pntd.0013693.ref006","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"PN Levett","year":"2001","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0013693.ref007","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-662-45059-8_5","volume-title":"Leptospirosis in humans, in: Adler B, editor. 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