Soutenance de thèse : Julien ORLANS

Structural and functional characterization of PGRP-LB: modulation of the IMD immune pathway in pathogenic and mutualistic bacterial interactions

Doctorant : Julien ORLANS

Laboratoire INSA : BF2I

Ecole doctorale : ED 341 : Evolution, Ecosystèmes, Microbiologie, Modélisation

Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play a pivotal role in innate immunity. These proteins have been characterized at various levels of the immune process as receptors, modulators, and effectors. Because of this substantial functional and taxonomic diversity, PGRP classification and immune role identification can be challenging. To address this question, in the first chapter of this thesis I used sequence similarity network method to propose a new approach in the analysis of PGRPs. This study allowed me to identify the key residues and the protein features involved in the PGRPs diversification. However, this analysis pointed to the low characterization of the PGRP modulators of the immunity compared to the PGRP receptors. In order to widen our knowledge on the PGRPs, I focused on the immunomodulator PGRP-LB, which is able to cleave peptidoglycan (PGN) into non- immunogenic compounds. In the second chapter, I deciphered the reaction mechanism of amidase PGRPs, using enzymatic assays and X-ray crystallography on the Drosophila PGRP-LB. Finally, in the third chapter, I studied how the pgrp-lb gene expression and activity have evolved under endosymbiotic constraints in the association between the weevil Sitophilus spp. and the intracellular bacterium Sodalis pierantonius. The results obtained during this PhD showed the large diversification of the PGRPs in the adaptation of the innate immunity.