Two-component systems (TCSs) are signal transduction pathways present in bacteria, fungi and plants. Different TCSs sense a wide variety of signals and trigger regulatory responses that control important biological phenomena, including virulence mechanisms in pathogenic bacteria. TCSs are composed of two proteins: a sensory histidine kinase (HK) and a response regulator (RR). HemK-HemR (or HemKR) is a relevant TCS from Leptospira spp., a genus spanning saprophytic (e.g. L. biflexa) and pathogenic (e.g. L. interrogans) species. Growth of hemKR- KO mutants is severely affected in the absence of hemin or δ-aminolevulinic acid, indicating its relevance in controlling heme metabolism.
We have also previously shown that HemR is able to activate and repress the expression of downstream target genes, several of which encode enzymes involved in heme metabolism. HemK-mediated HemR phosphorylation results in increased transcription of genes coding for heme-biosynthesis enzymes like HemA, while simultaneously, repressing genes encoding heme-degradation enzymes such as the heme oxygenase HmuO. It has also been shown that HmuO is a virulence factor in pathogenic Leptospira. So far, the specific signal detected by HemK remains unknown. This transcriptomics proposal is embedded in a broader project in collaboration with the Buschiazzo lab at IPMontevideo, with the general aim of uncovering The HemKR physiologic signal(s).
