The structural and functional basis of reprogramming of vesicular transport by Salmonella enterica effector proteins
Final Report Abstract
The project 'The structural and functional basis of reprogramming of vesicular transport by Salmonella enterica effector proteins' was directed to understand the molecular mechanism of host cell manipulation during the intracellular lifestyle of Salmonella enterica in mammalian host cells. Focus of the project was on the function of effector proteins of the Salmonella Pathogenicity Island 2-endoced type III secretion system (SPI2-T3SS). We investigated the structure function-relationship of SifA and SseF as two SPI2-T3SS effectors with prominent roles in the remodeling of the host cell endosomal system. This led to the identification of domains and residues that are functionally relevant in these effectors. The identification of host cell factors directly interacting with selected effector proteins by genetic screens or protein pull-down was not possible. However, we devised a proteomics based analysis of 'Salmonella-modified membranes' in infected host cells. The proteome signatures allowed the identification of the subcellular origin of membranes of the Salmonella-containing vacuole (SCV) and Salmonella-induced filaments (SIF). Furthermore, a siRNA interference screen was performed and resulted in identification of several host cell factors required for the formation of SIF. Using a live cell imaging approach, we investigated the contribution of the various SPI2-T3SS effector proteins. Novel roles of SseF, SseG and PipB2 in remodeling of SMM were observed. In the continuation of the project, the ultrastructure of SMM was determined.
Publications
- (2011) Cellular aspects of immunity to intracellular Salmonella enterica. Immunol. Rev. 240, 185-195
Jantsch, J, Chikkaballi, D. and Hensel, M.
(See online at https://doi.org/10.1111/j.1600-065X.2010.00981.x) - (2012) (2012) Functional characterization of Salmonella Pathogenicity Island 2-effector protein SseF. PLoS One 7, e35004
Müller, P. and Hensel, M.
- (2012) SseF, a type III effector protein from the mammalian pathogen Salmonella enterica, requires resistance-gene mediated signalling to activate cell death in the model plant Nicotiana benthamiana. New. Phytol. 194, 1046-1060
Üstün, S., Palmisano, R., Müller, P., Hensel, M. and Börnke, F.
(See online at https://doi.org/10.1111/j.1469-8137.2012.04124.x) - (2014). Live cell imaging reveals novel functions of Salmonella enterica SPI2-T3SS effector proteins in remodeling of the host cell endosomal system. PLoS One 9, e115423
Rajashekar, R., Liebl, D., Chikkaballi, D., Liss, V., and Hensel, M.
(See online at https://doi.org/10.1371/journal.pone.0115423)
