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It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of\n            <jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>\n            during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in\n            <jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>\n            . In this pathway, EbpA, a \u03c3\n            <jats:sup>54<\/jats:sup>\n            activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (\u03c3\n            <jats:sup>54<\/jats:sup>\n            ) control expression of at least three genes, encoding AmtB (an ammonium transport protein) and two proteins of unknown function. Electrophoresis mobility shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter region and upstream of these three identified genes, respectively. Genetic disruption of\n            <jats:italic>ebpA<\/jats:italic>\n            in\n            <jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>\n            serovar Manilae virtually abolished expression of the three genes, including\n            <jats:italic>amtB<\/jats:italic>\n            in two independent\n            <jats:italic>ebpA<\/jats:italic>\n            mutants. Complementation of the\n            <jats:italic>ebpA<\/jats:italic>\n            mutant restored expression of these genes. Intraperitoneal inoculation of gerbils with the\n            <jats:italic>ebpA<\/jats:italic>\n            mutant did not affect mortality. However, the\n            <jats:italic>ebpA<\/jats:italic>\n            mutant had decreased cell length\n            <jats:italic>in vitro<\/jats:italic>\n            and had a significantly lowered cell density at stationary phase when grown with\n            <jats:sc>l<\/jats:sc>\n            -alanine as the sole nitrogen source. Furthermore, the\n            <jats:italic>ebpA<\/jats:italic>\n            mutant has dramatically reduced long-term survival ability in water. Together, these studies identify a regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the zoonotic cycle of\n            <jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Leptospirosis is a reemerging disease with global importance. However, our understanding of gene regulation of the spirochetal pathogen\n            <jats:named-content content-type=\"genus-species\">Leptospira interrogans<\/jats:named-content>\n            is still in its infancy, largely due to the lack of robust tools for genetic manipulation of this spirochete. Little is known about how the pathogen achieves its long-term survival in the aquatic environment. By utilizing bioinformatic, genetic, and biochemical methods, we discovered a regulatory pathway in\n            <jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>\n            , the EbpA-RpoN pathway, and demonstrated that this pathway plays an important role in environmental survival of this pathogen.\n          <\/jats:p>","DOI":"10.1128\/aem.02377-16","type":"journal-article","created":{"date-parts":[[2016,11,19]],"date-time":"2016-11-19T03:25:36Z","timestamp":1479525936000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment"],"prefix":"10.1128","volume":"83","author":[{"given":"Wei-Lin","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China"},{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Pappas","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 Biologie des Spiroch\u00e8tes, Paris, France"},{"name":"Manhattanville College, Department of Biology, Purchase, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 Biologie des Spiroch\u00e8tes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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