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Here, we use a recently described lineage of environmental-adapted leptospires, which are evolutionarily the closest relatives of the highly virulent\n                    <jats:italic>Leptospira<\/jats:italic>\n                    species, to explore the key phenotypic traits and genetic determinants of\n                    <jats:italic>Leptospira<\/jats:italic>\n                    virulence. Through a comprehensive approach integrating phylogenomic comparisons with\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    phenotyping studies, we show that the evolution towards pathogenicity is associated with both a decrease of the ability to survive in the environment and the acquisition of strategies that enable successful host colonization. This includes the evasion of the mammalian complement system and the adaptations to avoid activation of the innate immune cells by the highly-virulent\n                    <jats:italic>Leptospira<\/jats:italic>\n                    species (also called P1+ species), unlike other species belonging to the phylogenetically related P1- and P2 groups, as well as saprophytes. Moreover, our analysis reveals specific genetic determinants that have undergone positive selection during the course of evolution in\n                    <jats:italic>Leptospira<\/jats:italic>\n                    , contributing directly to virulence and host adaptation as demonstrated by gain-of-function and knock-down studies. Taken together, our findings define a new vision on\n                    <jats:italic>Leptospira<\/jats:italic>\n                    pathogenicity, identifying virulence attributes associated with clinically relevant species, and provide insights into the evolution and emergence of these life-threatening pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012161","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T13:34:43Z","timestamp":1721223283000},"page":"e1012161","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Evolutionary insights into the emergence of virulent Leptospira spirochetes"],"prefix":"10.1371","volume":"20","author":[{"given":"Alexandre","family":"Giraud-Gatineau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Nieves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke B.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Benaroudj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric J.","family":"Veyrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-5579","authenticated-orcid":true,"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"ppat.1012161.ref001","doi-asserted-by":"crossref","first-page":"e0003898","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":"ppat.1012161.ref002","first-page":"351","article-title":"Ending the Neglect of Treatable Bacterial Zoonoses Responsible for Non-Malaria Fevers","volume":"94","author":"C Goarant","year":"2021","journal-title":"Yale J Biol Med"},{"key":"ppat.1012161.ref003","doi-asserted-by":"crossref","DOI":"10.3389\/frwa.2023.1195094","article-title":"Leptospirosis: Towards a Better Understanding of the Environmental Lifestyle of Leptospira","volume":"5","author":"G Davignon","year":"2023","journal-title":"Frontiers in Water"},{"key":"ppat.1012161.ref004","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrmicro.2017.5","article-title":"Virulence of the zoonotic agent of leptospirosis: still terra incognita?","volume":"15","author":"M. 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