Skip to main content
Article thumbnail
Location of Repository

Streptococcus pneumoniae Deficient in Pneumolysin or Autolysin Has Reduced Virulence in Meningitis

By Robert A. Hirst, Bejal Gosai, Andrew Rutman, Christopher J. Guerin, Pierluigi Nicotera, Peter W. Andrew and Christopher L. O'Callaghan

Abstract

Background: The role played by pneumolysin and autolysin in pneumococcal meningitis is poorly understood.\ud Method: A rat model was used to investigate the disease, in which surgical implantation of a cisternal catheter allowed bacterial instillation and cerebrospinal fluid (CSF) sampling.\ud Results: CSF infection of rats with wild-type pneumococci caused meningitis within 26 h, whereas isogenic mutants that do not express pneumolysin (∆Ply) or autolysin (LytA ¯) caused very mild or no disease. Wild-type infections resulted in pneumococci in the CSF and cortical homogenates, but a minority of the rats infected with ∆Ply or LytA ¯had bacteria in these locations at 26 h. Leukocyte numbers in the CSF were similar after infection with all\ud pneumococci; however, neutrophils and monocytes predominated after wild-type infection, whereas lymphocytes and atypical lymphocytes predominated after infection with the mutants. Wild-type pneumococci caused disruption to the ependyma, but this was not observed in rats infected with ∆Ply or LytA ¯. Cells surrounding the ventricles in wild type–infected animals expressed caspase 3, and astrocytes had hypertrophy; both findings were absent in rats infected with the mutants.\ud Conclusions: This study provides strong in vivo evidence that pneumolysin and autolysin play crucial roles in the pathogenesis of pneumococcal meningitis

Publisher: University of Chicago Press
Year: 2008
DOI identifier: 10.1086/527322
OAI identifier: oai:lra.le.ac.uk:2381/8859
Journal:

Suggested articles

Citations

  1. (1995). A pneumolysin-negative mutant of Streptococcus pneumoniae causes chronic bacteremia rather than acute sepsis in mice. Infect Immun
  2. (2000). Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect Immun doi
  3. (1999). Andrew PW,Hirst RA,O’CallaghanC. The effect of the pneumococcal toxin, pneumolysin on brain ependymal cilia. Microb Pathog doi
  4. (1997). C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro.
  5. (1985). Cerebrospinal fluid cytopathology. Clin Lab Med
  6. (2000). Changing epidemiology of bacterial meningitis in the United States. Curr Infect Dis Rep doi
  7. (2006). Circulatingmonocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice. Brain doi
  8. (2002). Cognitive impairment in adults with good recovery after bacterial meningitis. doi
  9. (2002). Decreased virulence of a pneumolysindeficient strain of Streptococcus pneumoniae in murine meningitis. Infect Immun doi
  10. (1998). Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis. doi
  11. (2000). Effect of pneumolysin on rat brain ciliary function: comparison of brain slices with cultured ependymal cells. Pediatr Res doi
  12. (1987). Ependyma of the rat fourth ventricle and central canal: response to injury. Acta Anat (Basel) doi
  13. (1998). Ependymal development, proliferation, and functions: a review. Microsc Res Tech doi
  14. (1995). Ependymal reactions to injury: a review.
  15. (2004). Hirst RA,Mohammed BJ,Mitchell TJ, Andrew PW,O’Callaghan C. Streptococcus pneumoniae-induced inhibitionof rat ependymal cilia is attenuated by antipneumolysin antibody. Infect Immun doi
  16. (1988). Insertional inactivation of the major autolysin gene of Streptococcus pneumoniae.
  17. (2001). Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ doi
  18. (1985). MortonDB,Griffiths PH.Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. Vet Rec doi
  19. (2002). Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci doi
  20. (1999). Paton JC.Comparative virulence of Streptococcus pneumoniae strains with insertion-duplication, point, and deletion mutations in the pneumolysin gene. Infect Immun
  21. (1993). Pneumococcal bacteraemia and meningitis in England andWales,
  22. (2002). Pneumococcal pneumolysin and H2O2mediate brain cell apoptosis duringmeningitis.
  23. (2001). Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae. Infect Immun doi
  24. (2000). Relative roles of pneumolysin and hydrogen peroxide from Streptococcus pneumoniae in inhibition of ependymal ciliary beat frequency. Infect Immun doi
  25. (2003). Streptococcus pneumoniae damages the ciliated ependyma of the brain during meningitis. Infect Immun doi
  26. (1978). The circulating “atypical” lymphocyte. Hum Pathol doi
  27. (1995). The ependyma: a protective barrier between brain and cerebrospinal fluid. Glia doi
  28. (1999). The epidemiology of pneumococcal infection in children in the developing world. doi
  29. (2001). The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis. doi
  30. (1995). The limited role of pneumolysin in the pathogenesis of pneumococcal meningitis. doi
  31. (1997). The pneumococcal cell wall degrading enzymes: amodular design to create new lysins?MicrobDrug Resist doi
  32. (1995). The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus. doi
  33. (2004). The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol doi
  34. (2000). Twelve year outcomes following bacterial meningitis: further evidence for persisting effects. Arch Dis Child doi
  35. (2002). Upper and lower respiratory tract infection by Streptococcus pneumoniae is affected by pneumolysin deficiency and differences in capsule type. Infect Immun doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.