The effect of the pneumococcal toxin, pneumolysin on brain ependymal cilia

• Published in: Microbial pathogenesis Vol. 27; no. 5; pp. 303 - 309
• Main Authors: Mohammed, B.J, Mitchell, T.J, Andrew, P.W, Hirst, R.A, O»Callaghan, C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.1999; Elsevier
• Subjects: Animals; Bacterial Proteins; Bacteriology; Biological and medical sciences; Cilia - drug effects; Cilia - physiology; cilia, brain ependymal cilia, meningitis, pneumolysin; Cytotoxins - genetics; Cytotoxins - toxicity; Dose-Response Relationship, Drug; Ependyma - drug effects; Ependyma - ultrastructure; ependymal; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Microbiology; Microscopy, Electron, Scanning; Mutation; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; pneumolysin; Rats; Rats, Wistar; Streptococcus pneumoniae; Streptolysins - genetics; Streptolysins - toxicity; cilia, brain ependymal cilia, meningitis, pneumolysin; Nervous system diseases; Rat; Rodentia; Central nervous system; Host agent relation; Ciliated cell; In vitro; Streptococcus pneumoniae; Pathogenicity; Pneumolysin; Streptococcaceae; Toxin; Vertebrata; Mammalia; Central nervous system disease; Frequency beat; Bacteria; Micrococcales; Cytopathology; Meningitis; Ependyma; Cilia; Brain (vertebrata)
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1006/mpat.1999.0306

Densely ciliated ependymal cells cover the ventricular surface of the brain and cerebral aqueducts separating cerebrospinal fluid, which is infected in meningitis, from neuronal tissue. We have established an ex vivo model that allows measurement of ependymal ciliary beat frequency, using high-speed video analysis, during incubation with bacterial toxins. Ciliated ependyma, from Wistar rats, was exposed to the pneumococcal toxin, pneumolysin, and a mutant form with markedly reduced cytotoxic activity (0.1%). Wild-type pneumolysin (1500 HU/ml and 150 HU/ml: 10 and 1 μg/ml) caused rapid ciliary stasis (30–150 s), sloughing of cilia and cytoplasmic extrusion. Ciliary slowing before stasis was seen at 15 HU/ml (0.1 μg/ml); however, no effect on ciliary beat frequency was seen at lower concentrations (1.5 HU/ml and 0.15 HU/ml: 0.01 and 0.001 μg/ml). Mutant pneumolysin, 99.9% deficient in haemolytic activity, caused rapid ciliary stasis at 10 μg/ml but no effect was seen at lower concentrations (1–0.1 μg/ml). Pneumolysin, at levels which may be produced during severe pneumococcal meningitis, may cause rapid ependymal ciliary stasis.