A putative regulatory genetic locus modulates virulence in the pathogen Leptospira interrogans
Résumé
Limited research has been conducted on the role of transcriptional regulators in relation to virulence in L. interrogans, the etiological agent of leptospirosis. Here, we identify an L. interrogans locus that encodes for a sensor protein, an anti-sigma factor antagonist and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This mutant (lb139-) displayed attenuated virulence in the hamster model of infection and reduced motility in vitro. Whole transcriptome analyses using RNA-Sequencing, revealed down regulation of 115 and up regulation of 28 genes, with an over representation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localised to the extracellular space. Another significant finding encompassed suppressed expression of the majority of genes previously demonstrated to be up regulated at physiological osmolarity, including sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to loss of native expression of this genetic locus.