Objetivo The innovations of this project are the 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 imposes a huge disease burden on humans: it is the number one cause of pneumonia and it is the sed 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 or neurological damage after meningitis, due to the acute toxaemia. The first event in toxaemia is release of pro-inflammatory or toxic pneumococcal products, probably exacerbated by antibiotics. The pneumococcal toxin pneumolysin fulfils both definitions: it is directly toxic to mammalian cells and it stimulates 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 will be a target of this project A sed target will be the cell surface proteinases involved in adhesion and invasion, which are important virulence factors for the pneumococcus. These proteins represent new targets and their validation as targets has been done. The new treatment will be based on binding peptides isolated from a series of large phage display libraries or based on small molecules identified by high throughput screening. Following screening of the phage libraries the most promising peptides will be evaluated on the basis of binding affinity and neutralising action in vitro. The peptides and small molecules will be formulated in chitosan for nasal delivery. Peptides and small molecules will be tested in animal models of pneumonia, bacteraemia and meningitis, with and without antibiotics. We present our preliminary data showing that a peptide can be used to treat pneumococcal disease. These data underline the capacity of the sortium to achieve the project objectives. Ámbito científico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesclinical medicinepneumologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistancemedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Palabras clave Antibiotic Resistance Formulation Meningitis Metalloproteinase Peptides Phage Display Pneumolysin Pneumonia Strreptococccus Programa(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Tema(s) LSH-2003-2.1.2-3 - Novel approaches to address antimicrobial resistance through non-antimicrobial based therapies Convocatoria de propuestas FP6-2003-LIFESCIHEALTH-I Consulte otros proyectos de esta convocatoria Régimen de financiación STIP - Specific Targeted Innovation Project Coordinador UNIVERSITY OF LEICESTER Aportación de la UE Sin datos Dirección University Road LEICESTER Reino Unido Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo UNIVERSITA DEGLI STUDI DI SIENA Italia Aportación de la UE Sin datos Dirección Via Banchi di Sotto 55 SIENA Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos UNIVERSITÀ DEGLI STUDI DI MESSINA Italia Aportación de la UE Sin datos Dirección Piazza Pugliatti 1 MESSINA Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos ARCHIMEDES DEVELOPMENT LTD Reino Unido Aportación de la UE Sin datos Dirección Nottingham Science. & Technology Park, University Boulevard NOTTINGHAM Ver en el mapa Coste total Sin datos ESSAIS CLINIQUES-EVALUATION-EPIDÉMIOLOGIE-STATISTIQUES Francia Aportación de la UE Sin datos Dirección 49 rue Auguste Lançon PARIS Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos
