Victoria University

Identifying Human Host Cell Protein Targets of the Bartonella Effector Protein (Bep) Fic Domains

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dc.contributor.advisor Mackichan, Joanna Trounson, Vaughan 2016-10-05T03:18:07Z 2016-10-05T03:18:07Z 2016 2016
dc.description.abstract The genus Bartonellae represents an increasing number of emerging bacterial pathogens that utilises an unusual infection strategy, parasitising the red blood cells of their mammalian host. The most common species to infect humans are B. henselae and B. quintana. B. henselae is transmitted between cats by the cat flea, although occasionally infects humans via cat scratches or bites, causing cat-scratch disease (CSD). CSD is characterised by enlarged tender lymph nodes and fever. B. henselae also infects the endothelial cells of both its hosts; likely a factor in disease progression. B. quintana, the cause of trench fever during WWI, is spread people by the body louse. Trench fever is characterised by relapsing fever, headache, and bone pain. B. quintana is also able to infect human endothelial cells. These bacteria secrete a range of Bartonella effector proteins (Beps) via a Type IV secretion system, directly into endothelial cells, subverting host cell processes and resulting in internalisation of the bacteria. Beps have a range of functions, many of which are not fully characterised. B. henselae secretes three Beps (BepA-C) that contain a filamentation induced by cAMP (Fic) domain and a Bartonella Intracellular Delivery (BID) domain, with BepA being the best studied. BepA’s BID domain is responsible for intracellular delivery as well as inhibition of apoptosis by the host cell, however the exact function of the Fic domain remains unknown. Fic-containing bacterial toxins catalyse the transfer of an AMP moiety from ATP onto a host cell protein. This AMPylation frequently inactivates these proteins resulting in disrupted host cell processes and cytotoxicity. BepA has previously been shown to possess AMPylation activity, although the host target protein(s) are unknown. Evidence suggests that these proteins are novel targets. The aim of this study was to create protein constructs containing these Fic domains, and to develop techniques to identify the host cell target proteins post AMPylation. To this end, both a fluorescent ATP analogue and a fluorescent click chemistry based approach were utilised. While no target protein was identified, a basic methodology was developed for protein production and target protein identification that could be further developed. en_NZ
dc.language.iso en_NZ
dc.publisher Victoria University of Wellington en_NZ
dc.subject Bartonella henselae en_NZ
dc.subject AMPylation en_NZ
dc.subject Protein Purification en_NZ
dc.subject Adenylylation en_NZ
dc.subject Fic Domain en_NZ
dc.subject Protein expression en_NZ
dc.title Identifying Human Host Cell Protein Targets of the Bartonella Effector Protein (Bep) Fic Domains en_NZ
dc.title.alternative Identifying Human Host Cell Protein Targets of the Bep Fic Domains en_NZ
dc.type text en_NZ
vuwschema.contributor.unit School of Biological Sciences en_NZ
vuwschema.contributor.unit Centre for Biodiscovery en_NZ
vuwschema.type.vuw Awarded Research Masters Thesis en_NZ Biomedical Science en_NZ Victoria University of Wellington en_NZ Masters en_NZ Master of Biomedical Science en_NZ
dc.rights.license Creative Commons GNU GPL en_NZ
dc.rights.license Allow modifications, as long as others share alike en_NZ 2016-09-15T01:17:54Z
vuwschema.subject.anzsrcfor 060501 Bacteriology en_NZ
vuwschema.subject.anzsrctoa 1 PURE BASIC RESEARCH en_NZ

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