{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:39:26Z","timestamp":1761745166605,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802021","81671974","81760366,","81971951"],"award-info":[{"award-number":["81802021","81671974","81760366,","81971951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Medical and Health Science and Technology Project of China","award":["2019KY013"],"award-info":[{"award-number":["2019KY013"]}]},{"name":"Research Initiation Fund of Zhejiang People\u2019s Hospital in China","award":["ZRY2018B004"],"award-info":[{"award-number":["ZRY2018B004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Leptospirosis is a global zoonotic infectious disease caused by Leptospira interrogans. The pathogen rapidly invades into hosts and diffuses from bloodstream into internal organs and excretes from urine to cause transmission of leptospirosis. However, the mechanism of leptospiral invasiveness remains poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Proteolytic activity of M16-type metallopeptidases (Lep-MP1\/2\/3) of L. interrogans was determined by spectrophotometry. Expression and secretion of Lep-MP1\/2\/3 during infection of cells were detected by quantitative reverse-transcription polymerase chain reaction, Western blot assay, and confocal microscopy. Deletion and complementation mutants of the genes encoding Lep-MP1\/2\/3 were generated to determine the roles of Lep-MP1\/2\/3 in invasiveness using transwell assay and virulence in hamsters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Leptospira interrogans but not saprophytic Leptospira biflexa strains were detectable for Lep-MP-1\/2\/3-encoding genes. rLep-MP1\/2\/3 hydrolyzed extracellular matrix proteins, but rLep-MP1\/3 displayed stronger proteolysis than rLep-MP2, with 123.179\/340.136 \u03bcmol\/L Km and 0.154\/0.159 s-1 Kcat values. Expression, secretion and translocation of Lep-MP1\/2\/3 during infection of cells were increased. \u0394MP1\/3 but not \u0394MP2 mutant presented attenuated transmigration through cell monolayers, decreased leptospiral loading in the blood, lungs, liver, kidneys, and urine, and 10\/13-fold decreased 50% lethal dose and milder histopathologic injury in hamsters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Lep-MP1 and 3 are involved in virulence of L. interrogans in invasion into hosts and diffusion in vivo, and transmission of leptospirosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa176","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T11:08:32Z","timestamp":1586344112000},"page":"1008-1020","source":"Crossref","is-referenced-by-count":6,"title":["M16-Type Metallopeptidases Are Involved in Virulence for Invasiveness and Diffusion of Leptospira interrogans and Transmission of Leptospirosis"],"prefix":"10.1093","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3182-1077","authenticated-orcid":false,"given":"Yu-Mei","family":"Ge","sequence":"first","affiliation":[{"name":"Centre of Laboratory Medicine, Zhejiang Provincial People\u2019s Hospital, Affiliated Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People\u2019s Republic of China"},{"name":"Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai-Hua","family":"Sun","sequence":"additional","affiliation":[{"name":"Faculty of Basic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Ojcius","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Dentistry, University of the Pacific, San Francisco, California, USA"},{"name":"Universit\u00e9 de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, Guizhou, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Lin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu\u2019ai","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People\u2019s Republic of 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