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Title: Characterisation of the pathogenic Escherichia coli type three secretion system effector NleG
Author: McGeever, Bevin
ISNI:       0000 0004 6496 2014
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Enteropathogenic and enterohaemorrhagic E. coli are widely prevalent as the causative agents of diarrhoeal disease globally. Pathogenesis is mediated by injection of effector proteins by a Type III Secretion System (T3SS) into the cytosol of host cells. Recently bioinformatics and secretome analysis has been used to expand the repertoire of effectors to include several novel T3SS secreted bacterial proteins. The largest family among these is the NleG family, with nine members in enterohaemorrhagic E. coli O157:H7 strain EDL933 alone. While there is significant sequence diversity between family members, conserved catalytic residues in the C terminus show structural homology to E3 ubiquitin ligases. Ubiquitination is the covalent attachment of ubiquitin to target proteins to label them for degradation, signalling, trafficking and regulation of DNA transcription. Several viruses and bacteria encode ubiquitin modulating enzymes to manipulate the host cell during infection. Currently there are no known targets for NleG. This study identifies host interacting partners for the NleG family through yeast two hybrid screening. An interaction between NleG and DDX60, a DNA helicase implicated in the innate immune response, and a distinct interaction with a key cell cycle regulator, CDC20, are investigated further.
Supervisor: Frankel, Gad Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral