{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:18:32Z","timestamp":1792167512359,"version":"4.4.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"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":["R01AI112920, R21AI147573, R01AI118799, R01AI121217"],"award-info":[{"award-number":["R01AI112920, R21AI147573, R01AI118799, R01AI121217"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Leptospirosis is an important cause of morbidity and mortality worldwide. Disease severity ranges from asymptomatic colonization to widespread hemorrhage and multiorgan dysfunction. The causative agents, <jats:italic>Leptospira<\/jats:italic> spp., are zoonotic Gram-negative spirochetes. One important step in pathogenesis is binding of bacterial adhesins to host components. Previously our laboratory identified two <jats:italic>L. interrogans<\/jats:italic> candidate adhesins, LIC11574 and LIC13411, that bind to VE-cadherin <jats:italic>in vitro<\/jats:italic>. In the current study, we demonstrate the ability of two strains of pathogenic <jats:italic>L. interrogans<\/jats:italic> to disrupt the localization of VE-cadherin, a protein important to maintaining inter-endothelial junctions. Purified MBP-LIC11574 and MBP-LIC13411 bind human dermal microvascular endothelial cells in a pattern reminiscent of VE-cadherin, but do not disrupt VE-cadherin localization. Genes encoding the candidate adhesins from pathogenic <jats:italic>Leptospira<\/jats:italic> were cloned in an overexpression vector and introduced into non-pathogenic <jats:italic>L. biflexa<\/jats:italic>, creating gain-of-function strains producing LIC11574 or LIC13411. Protein production and localization to the outer membrane were confirmed by Triton X-114 fractionation. Although these strains do not disrupt VE-cadherin localization, production of LIC13411 increases binding of non-pathogenic <jats:italic>Leptospira<\/jats:italic> to human endothelial cells and specifically to VE-cadherin. In a short-term murine model of infection, LIC13411 production led to increased burdens of the non-pathogen in the lung, liver, kidney, and bladder. These data confirm the role of LIC13411 as an adhesin in <jats:italic>Leptospira<\/jats:italic> spp. and implicate it in dissemination to multiple organs. Importantly, anti-adhesin therapy has been shown to have many benefits over classical antibiotics. Taken together, this work provides novel insight into the pathogenesis of <jats:italic>Leptospira<\/jats:italic> spp. and identifies LIC13411 as a potential prophylactic and therapeutic target.<\/jats:p>","DOI":"10.3389\/fcimb.2022.917963","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:42:15Z","timestamp":1658493735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Heterologous production of the adhesin LIC13411 from pathogenic Leptospira facilitates binding of non-pathogenic Leptospira in vitro and in vivo"],"prefix":"10.3389","volume":"12","author":[{"given":"Matthew C.","family":"Surdel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth L.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip N.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenifer","family":"Coburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1016\/j.ijantimicag.2010.06.012","article-title":"Estimating the burden of human leptospirosis","author":"Abela-Ridder","year":"2010","journal-title":"Int. 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