The interaction of bacteria with the respiratory mucosa in vitro and in vivo

Using a simple nasopharyngeal organ culture in which the mucosa is exposed to air, this thesis describes the interaction between two piliated and one non-piliated variants of Neisseria meningitidis and the interaction of a pneumolysin sufficient and deficient isogenic variant of Streptococcus pneumoniae with respiratory mucosa. Piliated N. meningitidis adhered more often than the non-piliated variant to the respiratory mucosa and demonstrated tropism for non-ciliated epithelial cells and only rarely adhered to mucus. In contrast, S.pneumoniae demonstrated tropism for mucus. Infection resulted in a change in the appearance of mucus, ciliary beat slowing and epithelial damage. To assess if other bacteria may impair mucociliary clearance by disorganising cilia the effect of pyocyanin, 1-hydroxyphenazine (1-HP) and rhamnolipid on the orientation of human ciliated cells was studied. Pyocyanin and 1-HP at pathophysiological concentrations caused ciliary slowing, dyskinesia and disorientation of the ciliary microtubular pairs. However, the orientation of basal feet did not change. Rhamnolipid at pathophysiologic concentrations caused ciliary slowing but neither dyskinesia or disorientation. Disorientation of ciliary beat as well as slowed CBF may contribute to the slowing of mucociliary clearance in vivo. To assess if ciliary disorientation occurs as an acquired and/or congenital abnormality, groups of patients with chronic upper respiratory tract inflammation due to infection and patients with the clinical features of primary ciliary dyskinesia but normal ciliary beat frequency and ciliary ultrastructure were studied. Ciliary disorientation was associated with slowing of nasomucociliary clearance. The clinical features, ciliary function studies and the ciliary orientation of eleven patients with the classical features of primary ciliary dyskinesia but with normal ciliary ultrastructure were assessed. The results suggests that ciliary disorientation alone does represent a new variant of primary ciliary dyskinesia