How does pneumococcal meningitis trigger brain-cell death?
Research archive
- Humboldt University, Berlin, Germany
- Researchers:
Dr Johann Braun, Professor Joerg Weber
- Project Number: 0011.0
- Category: Treatment
- Duration: 2001-2005
- Start Date: 01 January 2001
- Type: Lay summary
- View scientific version
An important step in developing new drugs to protect against brain damage from bacterial meningitis is to find out how the toxins that meningitis bacteria release kill brain cells. Pneumococcal bacteria produce very potent toxins, and this is why pneumococcal meningitis is more likely to kill or cause brain damage than other types of meningitis. Two of these toxins have already been identified.
We know that pneumococcal bacteria overbalance calcium levels within brain cells, causing damage to the cells' "energy factories" (mitochondria). In turn, damaged mitochondria leak substances into the brain cells which make them self-destruct. This project will resolve which of the two known toxins is involved in this destruction, with the aim of identifying new targets for therapies to stop brain damage caused by meningitis.
Results from this study have been published in scientific journals as follows:
Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, Weber JR,
Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis.
J Clin Invest 2002 Jan;109(1):19-27.
http://www.jci.org/cgi/reprint/109/1/19.pdf
Weber JR, Moreillon P, Tuomanen EI,
Innate sensors for Gram-positive bacteria. Curr Opin
Immunol 2003 Aug;15(4):408-15.
http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VS1-48XCS2F-3-5&_cdi=6249&_user=10&_orig=search&_coverDate=08%2F31%2F2003&_qd=1&_sk=999849995&view=c&wchp=dGLbVzb-zSkzS&md5=f489b7ce5df8fde8a73faa47b287594c&ie=/sdarticle.pdf
Bermophl D, Halle A, Freyer D, Dagand E, Braun JS, Bechmann I, Schroder NWJ, Weber JR,
Research highlights: Medicine: Barrier grief. Nature 2005 June;435(7044):858. http://www.nature.com/nature/journal/v435858a.html
Bermpohl D, Halle A, Freyer D, Dagand E, Braun JS, Bechmann I, Schroder NW, Weber JR,
Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways.
J Clin Invest 2005 Jun;115(6):1607-15.
http://www.jci.org/cgi/reprint/115/6/1607.pdf
Hoffmann O, Zweigner J, Smith SH, Freyer D, Mahrhofer C, Dagand E, Tuomanen EI, Weber JR.
Interplay of pneumococcal hydrogen peroxide and host-derived nitric oxide.
Infect Immun. 2006 Sep;74(9):5058-66
http://iai.asm.org/cgi/reprint/74/9/5058
Rueter N, Freyer D, Bert B, Fink H, Weber JR.
Pneumococcal cell wall-induced meningitis impairs adult hippocampal neurogenesis. Hoffmann O, Mahrhofer C, Infect Immun. 2007 Sep;75(9):4289-97. Epub 2007 Jun 25
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17591796&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum