Determinants of survival and virulence of Campylobacter

Harvey, Philippa Caroline (2000). Determinants of survival and virulence of Campylobacter. PhD thesis The Open University.



The pathogenesis of Campylobacter 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 Campylobacter 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 mono layers. Translocation ability did not correlate with intracellular invasiveness, suggesting that different "invasion" phenotypes exist among Campylobacter isolates. Repeated exposure of Campylobacter isolates to Caco-2 cells caused an increase in their ability to invade and survive, which was associated with changes in protein expression. Campylobacter 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. jejuni 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 of the encoding genes, peb4A and htrB, were found to be essential for viability. Homologous recombination of an inactivated Ipx gene into the genome of C. jejuni caused increased sensitivity to H20 2, but did not affect the ability of C. jejuni to invade and survive within Caco-2 cell monolayers. This study demonstrated that isolates of Campylobacter differ significantly in their virulence potential with respect to their invasive phenotypes. In addition Campylobacter 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.

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