Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis

Johann S Braun, Jack E Sublett, Dorette Freyer, Tim J Mitchell, John L Cleveland, Elaine I Tuomanen, Joerg R Weber

Research output: Contribution to journalArticlepeer-review

248 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalJournal of Clinical Investigation
Issue number1
Publication statusPublished - Jan 2002


  • 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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