Characterisation of the interaction between Neisseria meningitidis and the human host
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