Virulence factors and cytosolic immunity

The ability of F. tularensis to cause disease is linked to its ability to replicate within the host cell cytoplasm. This replication requires the integrity of a region on Francisella chromosome termed the Francisella-pathogenicity Island, which is encoding an atypical type VI secretion system. The nature and the molecular functions of the effectors secreted by this type VI secretion system are largely unknown. We have characterized one of the protein of Francisella T6SS, IglG and demonstrated how it behaves as a PAAR-like protein. PAAR and PAAR-like proteins are seen as protein sharpening the spike of the T6SS and acting as cargo to translocate effectors into the target cells. We also characterized IglF as one protein interacting with this PAAR-like protein IglG, although it remains to be determined wether it is or not an effector! More in Rigard et al. Plos Pathogens 2016

We are aiming at identifying effectors and identifying their molecular function by developing several approaches ranging from structural biology to yeast-two hybrid assays. This project should lead to an understanding on how the bacterium hijack the host molecular machinery to replicate within the cytosol and should lead to identification of novel therapeutic targets.

In addition, to T6SS, we have a particular interest in understanding how Francisella goes largely undetected in the host. This led us in the past to study its atypical lipopolysaccharide in relation to inflammatory caspases in mice and men. Lagrange et al. Nat Com. 2018