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| Pneumococcal pneumolysin and H2O2 mediate brain cell apoptosis during meningitis |
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| Author(s): Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, Weber JR |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 109 Issue: 1 Pages: 19-27 Published: JAN 2002 |
| Times Cited: 116 References: 54 |
| 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 H2O2, eliminated mitochondrial damage and apoptosis. Purified pneumolysin or H2O2 induced microglial and neuronal apoptosis in vitro. Both toxins induced increases of intracellular Ca2+ and triggered the release of AIF from mitochondria. Chelating Ca2+ 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 H2O2 significantly reduced damage. Two bacterial toxins, pneumolysin and, to a lesser extent, H2O2, induce apoptosis by translocation of AIF, suggesting new neuroprotective strategies for pneumococcal meningitis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Tuomanen, EI (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA |
Addresses:
1. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA
2. Humboldt Univ, Univ Klinikum Charite, Dept Neurol, Berlin, Germany
3. Univ Glasgow, Div Infect & Immun, Glasgow, Lanark Scotland
4. St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA |
| Publisher: AMER SOC CLINICAL INVESTIGATION INC, 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: 509RZ |
| ISSN: 0021-9738 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |