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Pneumococcal pneumolysin and h2o2 mediate brain cell apoptosis during meningitis

Academic Article
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Overview

authors

  • Braun, J. S.
  • Sublett, J. E.
  • Freyer, D.
  • Mitchell, T. J.
  • Cleveland, John
  • Tuomanen, E. I.
  • Weber, J. R.

publication date

  • 2002

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Pneumococcus is the most common and aggressive cause of bacterial meningitis and induces a novel apoptosis-inducing factor-dependent (AIF-dependent) form of brain cell apoptosis. Loss of production of two pneumococcal toxins, pneumolysin and H(2)O(2), eliminated mitochondrial damage and apoptosis. Purified pneumolysin or H(2)O(2) induced microglial and neuronal apoptosis in vitro. Both toxins induced increases of intracellular Ca(2+) and triggered the release of AIF from mitochondria. Chelating Ca(2+) effectively blocked AIF release and cell death. In experimental pneumococcal meningitis, pneumolysin colocalized with apoptotic neurons of the hippocampus, and infection with pneumococci unable to produce pneumolysin and H(2)O(2) significantly reduced damage. Two bacterial toxins, pneumolysin and, to a lesser extent, H(2)O(2), induce apoptosis by translocation of AIF, suggesting new neuroprotective strategies for pneumococcal meningitis.

subject areas

  • Animals
  • Apoptosis
  • Apoptosis Inducing Factor
  • Bacterial Proteins
  • Calcium Signaling
  • Cells, Cultured
  • Flavoproteins
  • Humans
  • Hydrogen Peroxide
  • Membrane Proteins
  • Meningitis, Pneumococcal
  • Microglia
  • Microscopy, Electron
  • Models, Neurological
  • Rats
  • Streptococcus pneumoniae
  • Streptolysins
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci12035

PubMed ID

  • 11781347
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Additional Document Info

start page

  • 19

end page

  • 27

volume

  • 109

issue

  • 1

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