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Title: Pathogenesis of Bordetella bronchiseptica infection in canine respiratory tract air interface organ culture
Author: Anderton, T.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2003
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Bordetella pertussis and Bordetella parapertussis cause whooping cough in children and Bordetella bronchiseptica causes acute tracheobronchitis in dogs, commonly called kennel cough. Study of the molecular basis for Bordetella pathogenesis is hampered by the lack of infection models that use these pathogens in their natural hosts. The study of whooping cough is restricted by the exclusive infection of humans by B.pertussis, and kennel cough in dogs is limited by the difficulties associated with the use of dogs experimentally. Here I describe the development of a novel, physiologically relevant system for the maintenance of canine trachea at an air interface in vitro and its use for studying the pathogenesis of B. bronchiseptica. Wild-type B. bronchiseptica infection of the organ culture system mimics early in vivo events in that bacteria adhere to cilia, mucus production and ciliostasis are induced, and ciliated cells are damaged. Thus the model provides a physiologically relevant in vitro method for studying B.bronchiseptica pathogenesis. This model was utilised to probe the molecular basis for these events. B.bronchiseptica mutants deficient in the two-component regulatory system Bvg, filamentous haemagglutinin (FHA) or fimbriae (FIM) do not adhere to the organ culture model and do not induce pathology. Thus the bvg locus and more specifically the bvg-regulated factors, FHA and FIM are necessary for the attachment of bacteria to canine cilia, and this attachment may be necessary for the induction of subsequent pathology. A role for dermonecrotic toxin is also implicated in the induction of ciliostasis in canine trachea. The determination of the induction of cytokine expression by canine tissue in response to B.bronchiseptica infection was attempted but was unsuccessful. The significance of these findings in relation to whooping cough disease is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available