About
Pathogenic Leptospira lack many classical virulence factors and approximately 35% of their genome encode proteins of unknown function. Their virulence mechanisms and how they subvert the host and colonize tissues remain largely unknown. To understand the dynamic host-Leptospira interaction network that drives acute leptospirosis, we have determined the in vivo genome-wide transcriptional changes in both L. interrogans and hamster upon infection by Dual RNASeq.
Main feature of the host response to L. interrogans infection included an upregulation of genes involved in cell-cell junctions, cytoskeleton organization and endoplasmic reticulum stress response, highlighting that disruption of the cell-cell junction is one of the key features of Leptospira pathogenicity. Among the leptospiral genes highly expressed in the host, we identified two VM-encoding genes, whose inactivation resulted in the loss of virulence in the hamster model and decreased Main feature of the host response to L. interrogans infection included an upregulation of genes involved in cell-cell junctions, cytoskeleton organization and endoplasmic reticulum stress response, highlighting that disruption of the cell-cell junction is one of the key features of Leptospira pathogenicity. Among the leptospiral genes highly expressed in the host, we identified two VM-encoding genes, whose inactivation resulted in the loss of virulence in the hamster model and decreased cell-cell junctions disruption. Overall, this approach allows to explore the Leptospira-host interaction dynamics and reveals novel Leptospira virulence factors contributing to adaptation and dissemination in the host.
