Suzana Salcedo - Vendredi 27 octobre 2017 10h30
Auditorium - Bât. 442 - Séminaire Micalis
Bacterial TIR effectors and host immune evasion
Young Investigator FINOVI
Group leader of Cell Biology of Bacterial Pathogenicity teamLaboratory of Molecular Microbiology and Structural Biochemistry
CNRS UMR 5086 - University of Lyon
Bacterial pathogens have developed numerous strategies to subvert the innate immune system to establish an infection. Several bacterial pathogens take advantage of TIR domain-containing proteins for blocking Toll-like receptor (TLR) signalling but the mechanisms that enable these proteins to interfere with receptor proximal events are still poorly characterized. We have been studying bacterial TIR domain-containing proteins from the intracellular pathogen Brucella abortus (BtpA and BtpB) and more recently of the multi-drug resistant pathogen Pseudomonas aeruginosa PA7, that we called PumA. In the lab we aim at identifying their cellular targets and characterize their role during infection. By combining microbial genetics with cell biology and biochemistry approaches we have found these bacterial TIR proteins inhibit NFκB translocation into the nucleus during infection. In the case of PumA we found it directly interacts with the TLR adaptors but more interestingly it also targets a component of the endosomal-sorting complex required for transport I (ESCRT-I) called ubiquitin-associated protein 1 (UBAP1), an important modulator of cytokine receptor sorting.
In contrast, Brucella TIR-containing proteins are not targeting endosomal sorting but instead controlling host cytoskeletal functions. Overall, our studies suggest TIR domains are not only involved in standard TIR-TIR interactions key in innate immunity but also mediate targeting of alternative pathways relevant for bacterial pathogenesis.
Vendredi 27 octobre 2017
Auditorium - Bât. 442
INRA, Jouy en Josas
Invitée par Cristel Archambaud