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In bacteria, two\u2010component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two\u2010component systems in L<\/jats:italic><\/jats:styled-content>eptospira<\/jats:italic> are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two\u2010component system has been obtained so far only for the H<\/jats:styled-content>klep\/R<\/jats:styled-content>rlep pair. It is known that hklep<\/jats:italic><\/jats:styled-content>\/<\/jats:italic>rrlep<\/jats:italic><\/jats:styled-content> knockout strains of L<\/jats:italic><\/jats:styled-content>eptospira biflexa<\/jats:italic> result in haem auxotrophy, although their de novo<\/jats:italic> biosynthesis machinery remains fully functional. Haem is essential for L<\/jats:italic><\/jats:styled-content>eptospira<\/jats:italic>, but information about H<\/jats:styled-content>klep\/R<\/jats:styled-content>rlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename H<\/jats:styled-content>emK<\/jats:styled-content>\/H<\/jats:styled-content>emR<\/jats:styled-content>. The DNA H<\/jats:styled-content>emR<\/jats:styled-content>\u2010binding motif was determined, and found within the genomes of saprophyte and pathogenic L<\/jats:italic><\/jats:styled-content>eptospira<\/jats:italic>. In this way, putative H<\/jats:styled-content>emR<\/jats:styled-content>\u2010regulated genes were pinpointed, including haem catabolism\u2010related (hmuO<\/jats:italic><\/jats:styled-content> \u2013 haem oxygenase) and biosynthesis\u2010related (the hemA\/C\/D\/B\/L\/E\/N\/G<\/jats:italic><\/jats:styled-content> operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo<\/jats:italic>, inversely repressing the hmuO<\/jats:italic><\/jats:styled-content>, while activating the hemA<\/jats:italic><\/jats:styled-content> operon transcription. The crystal structure of H<\/jats:styled-content>emR<\/jats:styled-content> receiver domain was determined, leading to a mechanistic model for its dual regulatory role.<\/jats:p>","DOI":"10.1111\/mmi.12763","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T09:34:58Z","timestamp":1408700098000},"page":"340-352","source":"Crossref","is-referenced-by-count":13,"title":["H<\/scp>emR<\/scp> is an O<\/scp>mpR<\/scp>\/P<\/scp>hoB<\/scp>\u2010like response regulator from L<\/i><\/scp>eptospira<\/i>, which simultaneously effects transcriptional activation and repression of key haem metabolism genes"],"prefix":"10.1111","volume":"94","author":[{"given":"Natalia R.","family":"Morero","sequence":"first","affiliation":[{"name":"Institut Pasteur de Montevideo Unit of Protein Crystallography 2020 Mataojo 11400 Montevideo 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Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[{"name":"Institut Pasteur Biology of Spirochetes Unit 28, rue du Dr Roux 75015 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Buschiazzo","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo Unit of Protein Crystallography 2020 Mataojo 11400 Montevideo Uruguay"},{"name":"Institut Pasteur Dept of Structural Biology & Chemistry 25, rue du Dr Roux 75015 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"volume-title":"Experimentation: An Introduction to Measurement Theory and Experiment Design","year":"1962","author":"Baird 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