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Title: Intracellular targeting mechanisms of Salmonella virulence effector proteins, and bacterial interactions with host antigen presentation pathways
Author: Hutchinson, J. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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SPI2 effectors are responsible for an observed Salmonella-specified downregulation of MHC Class II at the surface of infected cells. The cooperative contribution of SPI2 effector interactions to the maturation of the Salmonella-containing vacuole (SCV) leads to the hypothesis that correct localisation of effectors following their secretion into the host cell is important to their function. Work described herein characterises the localisation of a key virulence factor, SifA, which contains a cysteine-rich C-terminal motif previously proposed to be a site for host lipid attachment. A role was demonstrated for lipid modification in retention of SifA at the SCV following secretion. However, membrane association and initial localisation of SifA to the SCV was shown to be independent of C-terminal lipid attachment, and instead likely dependent on the protein N terminus which shares homology with a subset of SPI2 effector N termini previously implicated in intracellular targeting. This thesis also characterises the distribution of host antigen presenting molecules within infected cells, drawing comparison between MHC Class II and the four surface isoforms of the non-classical lipid antigen-presenting CD1 molecules. Salmonella was shown to traffic through CD1-positive compartments yet in contrast to MHC Class II none of the CD1 isoforms were downregulated at the surface of infected MelJuso cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available