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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Salmonella virulence factors and their role in intracellular parasitism

Möst, Thomas 17 October 2014 (has links)
Salmonella est un pathogène intracellulaire dont la virulence dépend de la fonction de deux systèmes de sécrétion du type trois (T3SS). Les T3SSs sont responsables pour la transduction de protéines effectrices dans le cytoplasme de la cellule hôte afin d'initier l'invasion de la cellule et de former la vie intracellulaire de Salmonella. Plusieurs effecteurs forment la SCV et induisent un réseau de tubules qui est impliqué dans la stabilisation de la SCV. Il consiste de trois différents genres de tubules. Nous avons pu montrer que les protéines effectrices SseF et SseG sont responsables pour la formation d'un genre de ces tubules, les LAMP-1 negative tubules (LNTs). Leur fonction est importante puisque des souches de Salmonella qui induisent que des LNTs et ne pas d'autres tubules sont apte de créer une SCV stable. Ceci améliore la réplication et virulence in vivo comparé à des souches qui ne peuvent pas induire des tubules. En utilisant les LNTs comme modèle, nous avons essayé de comprendre la contribution des tubules à la formation de la SCV et aussi leurs interaction avec les endosomes tardives et les lysosomes (LE/lys). Nous avons découvert une contribution essentielle de la petite GTPase Arl8B à la fusion de tubules avec les LE/lys. Ainsi, le knockdown d'Arl8B réduit la capacité de reproduction de Salmonella dans la cellule hôte. Nous avons pu démontrer qu'une interaction entre l'effecteur SifA et Arl8B est responsable pour ces observations. / Salmonella is an intracellular pathogen, whose virulence relies on the function of two type three secretion systems (T3SSs). The T3SSs are responsible for the delivery of effector proteins into the host cell cytoplasm in order to mediate invasion of the cell and to shape Salmonella's intracellular life.Salmonella's intracellular survival and replication depends on its niche, the Salmonella containing vacuole (SCV), a compartment that is derived from host plasma membrane. Several effectors shape the SCV and give rise to a tubular network, which is implicated in the SCV's stabilization and consists of three different kinds of tubules. We were able to show that the effector proteins SseF and SseG play in concert to form one kind of tubules, the recently discovered LAMP-1-negative tubules (LNTs). Their function is important to Salmonella, as strains having only LNTs but none of the other tubules are able to create a stable SCV, which leads to better replication and virulence in vivo compared to a strain that lacks in tubule formation. Starting from these LNTs as working model, we tried to understand the contribution of tubules to the formation of the SCV and their interactions with the late endosomal / lysosomal compartment (LE/lys). We deciphered the small GTPase Arl8B to play an essential role in the fusion of tubules with LE/lys. Thereby, the knockdown of Arl8B reduced Salmonella's capability to replicate within host cells. We were able to show that an interaction between the effector SifA and Arl8B was responsible for our observations.

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