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Contribution à l'étude de l'assemblage du Système de Sécrétion de Type III de Shigella flexneri et à la caractérisation du rôle de la protéine IcsB dans l'autophagie

Abstract : Shigella flexneri is a gram-negative bacterium of the Enterobacteriaceae family, responsible for shigellosis or bacillary dysentery, an invasive colon disease that causes the death of one million individuals a year. Shigella has the ability to invade the colonic or rectal human mucosa, causing an intense inflammatory reaction by destroying the epithelium. Shigella owes its pathogenicity to the virulence plasmid that contains a mxi-spa region encoding the type III secretion system (SST3). The latter makes it possible to inject the effector proteins into the epithelial cells, which destabilizes the cellular signaling pathways in favor of the bacterium. My thesis project focused on the study of virulence factors encoded by genes located in the region of entry of the virulence plasmid. Two types of genes have been studied: 1 / a group of genes named spa: spa40, spa32, spa24, spa29 and spa9 whose products are important in the assembly and operation of SST3 and 2 / the gene icsB which codes for a effector secreted by the SST3 and allows Shigella to escape autophagy. Our experimental results have been the subject of three publications in international journals ("Molecular Microbiology", "Microbiology" and "Microbe and infection") including two as co-first author and one as first author. We have shown that: (1) the association of the proto-channel elements with Spa40 and its interaction with Spa32 plays an important role in the change of specificity of substrates: secretion of the components of the needle (MxiH and MxiI ) to that of the effectors, (2) the associations of the Spa24, Spa9 and Spa29 proto-channel elements with the Mxi-Spa components are important in the consolidation and operation of the export apparatus, (3) the interaction IcsB with host cell cholesterol allows Shigella to protect itself from autophagy. In conclusion, our work has elucidated some of the mysteries used by bacteria of the genus Shigella, namely the mode of assembly of the components of the base of the SST3 and the protection of Shigella against the autophagic cellular response. This work opens new perspectives for studying the SST3 system in other pathogenic bacteria. Secretion systems are conserved in many pathogenic bacteria for humans, animals and plants. Therefore, our contribution goes beyond the scope of Shigella and could lead to the development of new anti-infective drugs.
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Aimé Christian Kayath. Contribution à l'étude de l'assemblage du Système de Sécrétion de Type III de Shigella flexneri et à la caractérisation du rôle de la protéine IcsB dans l'autophagie. Biochimie, Biologie Moléculaire. Université de liège, 2010. Français. ⟨tel-01966960⟩

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