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Title: Characterisation of toxins produced by Campylobacter jejuni and related species
Author: Morris, Samantha J. S.
ISNI:       0000 0001 3424 5303
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2005
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During the last decade, Campylobacter jejuni has become recognised as one of the most common causes of human bacterial gastroenteritis in both the UK and the developing world, with over 46,000 cases of Campylobacter infection reported in England and Wales during 2002 alone. The actual number of cases is estimated to be nearer 354,000, and in addition, infection with C. jejuni has been linked to more severe conditions such as Guillain-Barré syndrome, reactive arthritis, and inflammatory bowel disease. However, despite nearly 30 years of research, the pathogenic mechanisms used to initiate disease have not been fully documented, and although it is accepted that C. jejuni produces a number of toxins, the current understanding is poorly defined and often contradictory. The aim of this research was to investigate and characterise these toxin(s), and to study potential toxins produced by the related pathogen Arcobacter butzleri, a recognised veterinary pathogen that recent research indicates may also be an important human pathogen. Cytotoxic effects were detected when cell free extracts of C. jejuni were applied to cultured cells in vitro, and it is suggested that most of this cytotoxicity was a result of LPS activity, either acting on its own, or complexed with the major outer membrane protein (MOMP). In addition, both C. jejuni and A. butzleri produced at least one haemolysin that was able to lyse equine erythrocytes in vitro. Characterisation of this activity has shown that the majority of the haemolysis was cell-associated, calcium dependent, partially destroyed by heat, and not regulated by iron. It was proposed that this was due to the activity of phospholipase A (PldA). A phospholipase A mutant was constructed from C. jejuni NCTC 11168 using inverse PCR mutagenesis. The mutant showed a markedly reduced haemolytic activity when tested in vitro, although not all of the activity was inhibited. It was demonstrated that PldA was responsible for the majority of the haemolysis detected, and the pldA gene was found to be highly conserved amongst a range of C. jejuni strains. It is likely that PldA is not the sole haemolytic factor in C. jejuni, and the remaining haemolytic activity may be due to a calcium independent, pore-forming toxin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available