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Title: Isolation and molecular characterisation of toxins from Campylobacter jejuni and related species
Author: Holmes, Kathryn
ISNI:       0000 0001 3580 7857
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2002
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Campylobacter jejuni is a major cause of food-borne infectious disease in the UK. Last year, approximately 54,000 cases of such diseases caused by C. jejuni were reported to the Communicable Disease Surveillance Centre (CDSC) for England and Wales. This level of infection exceeds that of other food poisoning organisms such as Salmonella. A significant level of research has been carried out in the last 20 years to try and elucidate the precise pathogenic mechanisms of C. jejuni, including the recent completion of the genome sequence of C. jejuni NCTC 11168. There is, however, a considerable amount that remains unknown about the mechanisms of disease and transmission of Campylobacter. Arcobacter is a newly emergent animal pathogen that is closely related to Campylobacter and was originally thought to belong in the genus Campylobacter. Very little is known about the pathogenic potential and mechanisms of Arcobacter spp. and its possible role as a human pathogen. Only one toxin, the cytolethal distending toxin, has been purified, sequenced and established as a component of the C. jejuni disease process. The production of many other toxins by C. jejuni has been reported but their significance in the disease process is unknown. Toxin production is thought to vary in response to various environmental and/or stress conditions and also between different strains of C. jejuni. Toxins are often proteinaceous in nature and either cell-associated or secreted from the bacterial cell to the target site. C. jejuni and Arcobacter strains were screened for toxicity using a methyl tetrazolium thiazolyl blue dye (MTT) cytotoxicity assay and haemolysis tests. All the organisms were shown to produce an oxygen-sensitive, cell-associated haemolysin. All C. jejuni strains were cytotoxic in the MTT assay, but C. jejuni NCTC 11351 demonstrated cytotoxicity from the broadest range of culture conditions. No cytotoxicity was detected in any of the Arcobacter strains using the MTT assay. Cytolethal distending toxin genes were detected in C. jejuni NCTC 11351 and a 55kDa outer membrane protein (OMP) from this strain also reacted strongly with cholera toxin monoclonal antibody. The cholera-reactive protein was partially purified and N-terminal sequence analysis revealed homology with the major outer membrane protein (MOMP) of Campylobacter. EPS complexes probably caused the cross-reactivity of this cytotoxic protein with cholera toxin antibody.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available