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Title: Characterisation of the interaction between Neisseria meningitidis and the human host
Author: Sim, Richard James.
ISNI:       0000 0001 3411 7985
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2002
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Neisseria meningitidis is an important cause of septicaemia and meningitis, yet can be found colonising the nasopharynx of up to 20% of healthy individuals. The aim of my work was to provide detailed characterisation of the cellular location of meningococcal carriage and subsequently select suitable models to investigate the molecular and cellular basis of the mechanisms by which the bacterium interacts with the human upper respiratory tract. This is the fundamental microbial-host interaction underlying the commensalism of Neisseria meningitidis. A survey of meningococcal carriage in tonsillar tissue was undertaken using IHe techniques that detect PorA, a protein unique to Neisseria meningitidis. This showed that carriage rates are higher than those described with nasopharyngeal swabbing, and that the bacterium occupies a site deep to the epithelium in the carrier state. To identify genes that are required to reach sub-epithelial sites, air-interface organ culture models were used to screen bacteria subjected to signature tagged mutagenesis. Ten potentially colonisation deficient mutants were isolated and further analysed. This is the first time that such a screen has been undertaken in tissue of human origin. Additionally, homologues of two genes essential for intracellular survival in Legionella pneumophila (macrophage infectivity potentiator and an unknown virulence protein) were identified in Neisseria meningitidis and mutants containing specific genetic deletions constructed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Human tonsillar tissue