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Most human cases of leptospirosis result from environmental infection. Biofilm formation and its contribution to the persistence of virulent leptospires in the environment or in the host have scarcely been addressed. Here, we examined spatial and time-domain changes in biofilm production by\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    . Our observations showed that biofilm formation in\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    is a highly dynamic process and leads to a polarized architecture. We notably found that the biofilm matrix is composed of extracellular DNA, which enhances the biofilm\u2019s cohesiveness. By studying\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    mutants with defective diguanylate cyclase and phosphodiesterase genes, we show that biofilm production is regulated by intracellular levels of bis-(3\u2032\u20135\u2032)-cyclic dimeric guanosine monophosphate (c-di-GMP) and underpins the bacterium\u2019s ability to withstand a wide variety of simulated environmental stresses. Our present results show how the c-di-GMP pathway regulates biofilm formation by\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    , provide insights into the environmental persistence of\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    and, more generally, highlight leptospirosis as an environment-borne threat to human health.\n                  <\/jats:p>","DOI":"10.1038\/s41522-020-0134-1","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T06:03:06Z","timestamp":1591941786000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-0088","authenticated-orcid":false,"given":"Roman","family":"Thibeaux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Estelle","family":"Soup\u00e9-Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malia","family":"Kainiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Girault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Bierque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8768-625X","authenticated-orcid":false,"given":"Julien","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"B\u00e4hre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Douy\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Eskenazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle","family":"Vinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-5579","authenticated-orcid":false,"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0690-9464","authenticated-orcid":false,"given":"Cyrille","family":"Goarant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"134_CR1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","volume":"3","author":"AR Bharti","year":"2003","unstructured":"Bharti, A. 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