Leptospirosis, caused by extracellular pathogenic Leptospira species, is the most widespread zoonotic disease globally, responsible for approximately one million severe cases and 60,000 deaths annually. Despite its significant impact, the mechanisms underlying Leptospira virulence remain poorly understood, as pathogenic Leptospira species lack many classical virulence factors. Notably, around 35% of the Leptospira genome encodes proteins with unknown functions, highlighting critical gaps in our knowledge of how these bacteria evade the host immune system and establish infections.
In our previous work, leveraging a transposon mutant library and gene expression analysis under in vivo conditions, we identified two histidine kinases as key regulators of Leptospira virulence. The current project aims to further elucidate the roles of these kinases in pathogenesis using targeted mutant strains. We will investigate their functional importance through phenotypic analyses and pathogenicity assays. To complement these studies, RNA-Seq analysis will be conducted both in bacterial culture and during host-cell interactions, comparing gene expression profiles between the mutant strains and the wild-type strain. This approach will provide insights into how these kinases contribute to the regulation of gene expression and the broader virulence mechanisms of Leptospira.
