Multiomics study to identify virulence factors of Rickettsia prowazekii revealed its adaptive mutation capabilities

We identified four virulence phenotypes of Rickettsia prowazekii (the deadly agent of epidemic typhus) that are associated with the upregulation of antiapoptotic genes (virulent strain) or the Interferon I pathway (avirulent). Transcriptional and proteomic analyses of R. prowazekii linked surface protein expression and methylation with virulence. By sequencing a virulent strain and using comparative genomics, we found hotspots of mutations in homopolymeric tracts of poly(A) and poly(T) that lead to gene split and inactivation and explain the loss of virulence in the vaccine strain. These areas of instability explains adaptive mutations leading to virulence recovery in the vaccine strain. Several approaches are combined including the transcriptome of endothelial cells (the target cells of Rickettsia prowazekii) in order to identify factors associated with virulence of Rickettsia prowazekii, the agent of epidemic typhus