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The mechanisms of jaundice caused by pathogenic <jats:italic><jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>eptospira<\/jats:italic> remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>eil's disease. In this work, we obtained three\u2010dimensional images of infected hamster livers using scanning electron microscope together with freeze\u2010cracking and cross\u2010cutting methods for sample preparation. The images displayed the corkscrew\u2010shaped bacteria, which infiltrated the <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>isse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and \u03b3\u2010glutamyl transpeptidase levels increased slightly, but not significantly. We also found in <jats:italic>ex vivo<\/jats:italic> experiments that pathogenic, but not non\u2010pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1\u00a0h after co\u2010incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.<\/jats:p>","DOI":"10.1111\/iep.12085","type":"journal-article","created":{"date-parts":[[2014,6,19]],"date-time":"2014-06-19T15:25:22Z","timestamp":1403191522000},"page":"271-281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Destruction of the hepatocyte junction by intercellular invasion of <i><scp>L<\/scp>eptospira<\/i> causes jaundice in a hamster model of <scp>W<\/scp>eil's disease"],"prefix":"10.1111","volume":"95","author":[{"given":"Satoshi","family":"Miyahara","sequence":"first","affiliation":[{"name":"Department of Bacteriology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsumasa","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Kanemaru","sequence":"additional","affiliation":[{"name":"Morphology Core Unit Kyushu University Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon Y. 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