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Title: Determinants of survival and virulence of Campylobacter
Author: Harvey, Philippa Caroline
Awarding Body: The Open University
Current Institution: Open University
Date of Award: 2000
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The pathogenesis ofCampy/abaeter enteritis is not well understood including the mechanisms involved in invasion and translocation across intestinal epithelial cells. The genetic make-up of the pathogen and its responses to different environmental cues are thought to contribute to the organism's ability to survive and cause disease. The extremes of environment which Campy/abaeter can with-stand, and the effect that this has on virulence and invasive ability remains undefined. For the first time, several isolates were compared quantitatively to determine the extent to which intracellular invasion contributes to translocation across epithelial cell monolayers. Translocation ability did not correlate with intracellular invasiveness, suggesting that different 'invasion' phenotypes exist among Campy/abaeter isolates. Repeated exposure ofCampy/abaeter isolates to Caco-2 cells caused an increase in their ability to invade and survive, which was associated with changes in protein expression. Campy/abaeter was grown in continuous culture under conditions of iron sufficiency, iron limitation, oxidative stress and low pH. Uniquely, growth under oxidative stress and iron replete conditions caused an increase in the invasive ability of C. jejlllli 81116, which was correlated with the up-regulation of specific proteins. The role of three proteins, HtrB, Tpx and PEB-4, was investigated at the molecular level. Two ofthe encoding genes, peb4A and htrB, were found to be essential for viability. Homologous recombination ofan inactivated tpx gene into the genome ofC. jejlllli caused increased sensitivity to HzOz, but did not affect the ability of C. jejulli to invade and survive within Caco-2 cell monolayers. This study demonstrated that isolates of Campy/abaeter differ significantly in their virulence potential with respect to their invasive phenotypes. In addition Campy/abaeter grown in well defined continuous culture conditions demonstrated for the first time the importance of iron and oxidative stress as acting as potenital cues for the expression of survival and invasion determinants.
Supervisor: Not available Sponsor: Not available
Qualification Name: Not available Qualification Level: Doctoral
EThOS ID:  DOI: Not available