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Title: Type III secretion in enteropathogenic Escherichia coli
Author: Singh, Mona P.
ISNI:       0000 0001 3415 7047
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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Type III secretion systems (T3SS) are complex multi-component structures that are utilised in two biological contexts: translocation ofbacterial effector proteins into eukaryotic cells and flagellar protein export. The two types ofT3SS share a conserved core set ofhomologous proteins which are integrated into a larger apparatus that includes a hol1'ow filamentous surface extension, which comprises the flagellar hook and filament, or the needle and the translocation apparatus in the case of flagellar or non-flagellar systems, respectively. Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are human gut pathogens that utilise a T3SS encoded by the locus of enterocyte effacement (LEE) and exploit a hollow filamentous extension to the needle, termed the EspA filament, for the passage of effector proteins directly from the bacterial cytoplasm into host cells. The mechanism of assembly ofthe EspA filament remains elusive, however similarities between the flagella and EspA filaments and their subunits allow comparisons to be drawn regarding their mechanism ofassembly. To this end, several aspects encompassing the structure, function and assembly ofthe EspA subunit and EspA filament were investigated in this study. Firstly the recently identified EspA N-terminal coiled coil domain was characterised, highlighting structural and stabilising roles in EspA filament assembly. Secondly, the potential for the EspA subunit to form an intra-subunit coiled-coil interaction and polymerise through inter-subunit interactions in a similar manner to flageIIin was illustrated. Thirdly, it was shown that there may be variation in the molecular basis of antigenic polymorphism displayed by EspA filaments between different EPEC and EHEC clonal lineages.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available