HemR is an OmpR/PhoB‐like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes. Issue 2 (15th September 2014)

• Record Type: Journal Article
• Authors: Morero, Natalia R.; Botti, Horacio; Nitta, Kazuhiro R.; Carrión, Federico; Obal, Gonzalo; Picardeau, Mathieu; Buschiazzo, Alejandro
• Is Part Of: Molecular microbiology. Volume 94:Issue 2(2014)
• Page Start: 340
• Page End: 352
• Publication Date: 2014-09-15
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12763
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Several <italic>L</italic><italic>eptospira</italic> species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two‐component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two‐component systems in <italic>L</italic><italic>eptospira</italic> are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two‐component system has been obtained so far only for the Hklep/Rrlep pair. It is known that <italic>hklep</italic><italic>/</italic><italic>rrlep</italic> knockout strains of <italic>L</italic><italic>eptospira biflexa</italic> result in haem auxotrophy, although their <italic>de novo</italic> biosynthesis machinery remains fully functional. Haem is essential for <italic>L</italic><italic>eptospira</italic>, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR‐binding motif was determined, and found within the genomes of saprophyte and pathogenic <italic>L</italic><italic>eptospira</italic>. In this way, putative HemR‐regulated genes were pinpointed, including haem catabolism‐related (<italic>hmuO</italic> – haem oxygenase) and biosynthesis‐related (the <italic>hemA/C/D/B/L/E/N/G</italic> operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed <italic>in vivo</italic>, inversely repressing the <italic>hmuO</italic>, while activating the <italic>hemA</italic> operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role.</p> </abstract>