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Virulence strategies of Campylobacter jejuni

By Lieke van Alphen

Abstract

Campylobacter jejuni is recognized as the leading cause of bacterial foodborne disease, causing approximately 400 million human cases of enterocolitis world wide each year. Many cases can be attributed to foreign travel, making it one of the most important causative agents of traveller's diarrhea. The pathogenicity of C. jejuni depends on its ability to attach to and invade human intestinal epithelial cells. Despite all the progress in the identification of virulence factors and invasion strategies of C. jejuni, the exact mechanisms of cellular infection by C. jejuni remain to be elucidated. Deciphering the cellular infection mechanism(s) is important as this may give direction and form the basis for the development of new strategies of infection-intervention and/or protection. The aim of the research described in this thesis was to explore virulence strategies of C. jejuni to further define the mechanism of invasion employed by the pathogen. The results presented in this thesis add a new exciting chapter to the wide array of C. jejuni virulence strategies. We provide evidence that a larger version of the adhesin CadF is expressed in C. coli compared to C. jejuni. This might play a role in the differences in virulence observed for these organisms and may be exploited in diagnostics to discriminate these species in food and clinical specimens. Furthermore, we have identified the role of the phase variable maf4 gene, which is shown to contribute to changes in the glycosylation of the surface exposed flagellum. This may be important in the evasion of the immune response towards C. jejuni. Perhaps the most exciting finding described in this thesis is the discovery of the novel route of C. jejuni invasion of epithelial cells. This invasion is characterized by active migration of bacteria underneath epithelial cells (termed subvasion) and subsequent highly efficient invasion of epithelial cells from the basolateral side. The discovery of this novel invasion route and particularly the high levels of intracellular bacteria resulting from invasion could contribute to resolving key steps in C. jejuni pathogenesis. Dissection of the taxis machinery of C. jejuni demonstrated the existence of a CheA-independent chemotaxis system, never reported before in prokaryotes. This system did rely on the chemotaxis proteins CheY and CheW and, surprisingly, the metabolic enzyme (SerB). This novel bacterial taxis system was shown to be the molecular mechanism driving the highly efficient cellular infection. It was most active under conditions of nutrient starvation. Under nutrient-rich conditions, C. jejuni displayed the classical CheA-dependent chemotaxis and was barely attracted to epithelial cells. In contrast, under nutrient poor conditions the CheA-independent taxis pathway directed the bacteria towards the epithelial cells. Collectively, our results indicate that C. jejuni can switch between two modes of taxis and that the CheA-independent bacterial starvation-controlled taxis system drives the pathogen towards the epithelial cells

Topics: Diergeneeskunde, Campylobacter, epithelium, infection, CadF, flagella, glycosylation, motility, virulence
Publisher: Utrecht University
Year: 2007
OAI identifier: oai:dspace.library.uu.nl:1874/25502
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