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PNEUMOPEP


New methods of treatment of antibiotic-resistant pneumococcal disease
EC contribution
: € 1.500.000
Duration
: 36 months
Starting date
: 01/06/2005
Funding scheme
: Specific Targeted Research Project
Keywords
: Pneumolysin, Streptococcus Pneumoniae, Protease
Contract/Grant agreement number
: LSHM-CT-2005-512099
Project web-site
: -

Background:

The advances of the PNEUMOPEP project were new targets, identification of completely new lead compounds, a new approach to adjunctive therapy and a new method of delivery of the compounds.

Streptococcus pneumoniae (S. pneumoniae) imposes a huge disease burden on humans: it is the number one cause of pneumonia and it is the second most common cause of meningitis. There is a pandemic of multi-drug resistant pneumococci and treatment is compromised. Even if antibiotics kill the bacterium, they can fail to prevent death from neurological damage after meningitis, due to the acute toxaemia.

The first event in toxaemia is the release of pro-inflammatory or toxic penumococcal products, probably exacerbated by antibiotics. The pneumococcal toxin pneumolysin fulfils both definitions: it is directly toxic to mammalian cells and it stimulates the release of inflammatory mediators from host cells.

For this reason and because the toxin is essential for the survival of the bacterium in vivo, pneumolysin was a target for this project. A second target was the cell surface proteinases involved in adhesion and invasion, which are important virulence factors for the pneumococcus. These proteins represented new targets and their validation as targets was completed.

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