Dynamic modification of microtubule-dependent transport by Salmonella effector proteins

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The intracellular pathogen Salmonella enterica utilizes a type III secretion system encoded by Salmonella Pathogenicity Island 2 to translocate effector proteins that manipulate infected host cells. We have recently identified SseF and SseG as two novel effector proteins that interfere with the host cell cytoskeleton. In contrast to most other effector proteins, SseF and SseG are not interacting with the actin cytoskeleton but are rather targeted to microtubules. We observed that translocation of SseF and SseG induces the bundling of microtubules, and affects the aggregation of endosomal vesicles along microtubules. These observations lead to the hypothesis that intracellular Salmonella modify the transport along microtubules in order to generate an intracellular niche that is permissive for bacterial proliferation. The proposed project aims to investigate the interaction of effector proteins SseF and SseG with microtubule functions in detail. Host cell proteins interacting with effector protein SseF and SseG will be identified by complementary molecular approaches. The molecular interactions will be studied in detail and functional domains of the SseF and SseG will be defined. It is also planned to establish functional assays to analyse the interference with microtubule-dependent transport functions. This project will ultimately contribute to the understanding of a novel form of host-pathogen interaction and reveal how normal eukaryotic cell functions are manipulated by bacterial virulence determinants.