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Subversion of the host cell by Shigella flexneri: the role of the type III secretion substrates OspB and OspC1 (SCHNUPF 2005 EIF)
Start date: Apr 3, 2008, End date: Apr 2, 2010 PROJECT  FINISHED 

Many gram-negative bacterial pathogens, including the intracellular human pathogen Shigella flexneri, use a dedicated secretion system, termed type III secretion (TTS) system, to inject bacterial proteins directly from the bacterium, across the host plasma membrane, into the host cell cytosol. The translocated bacterial effectors facilitate infection and virulence by manipulating host signalling pathways, including those regulating apoptosis, cytoskeletal rearrangements and cytokine production. Recently, a n umber of new effectors, named Osps (outer Shigella proteins), including OspB and OspC1, that are secreted by the TTS system of S. flexneri.We hypothesize that OspB and OspC1 are secreted into the invaded host cell to subvert the host cell response to bacterial infection and facilitate the disease process. To test this hypothesis we aim to characterize the function of OspB and OspC1 by:i. analysing the in vitro and in vivo phenotype of OspB and OspC1 deletion mutants,ii. following the fate of OspB and Osp C1 in the host cell, andiii. identifying cellular targets of OspB and OspC1.These experiments will lead to a greater understanding of the subversive mechanisms used by S. flexneri and other gram-negative pathogens to manipulate the host and cause disease.
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