Link to Pubmed [PMID] – 29600195
Front Cell Infect Microbiol 2018;8:45
Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of . In our comprehensive genomic analysis of 20 spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes and ) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of mutant strains with disruption of one () or both genes () revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that and evolved independently within different ecological lineages in via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium.