Objectif
Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and septicemia worldwide with a high case-fatality rate. Although penicillin remains the drug of choice in the treatment of IMD, an increasing number of meningococci with reduced susceptibility to penicillin have been emerging worldwide. Reduces susceptibility or resistance to penicillin in meningococci is connected to alterations in penicillin binding protein 2, PBP2. PBPs are involved in the late stages of peptidoglycan (PG) biosynthesis and therefore PBPs alterations might result in PG modifications and hence affect PG-dependent signalling. Until recently it was thought that N. meningitidis strains own only three PBPs, PBP1, PBP2 and PBP3. However, genomic analysis of the complete sequence of meningococcal strains revealed the presence of two other putative genes encoding PBP4 and PBP5 which can possess D,D-carboxypeptidase and endopeptidase activity. And indeed the results obtained during the previous Marie Curie IEF from the PG structure study as well as from animal model provide the first indication that putative PBP4 and PBP5 are functional in N. meningitidis, play a role in the PG synthesis and influence the virulence of meningococcal isolates. It has been proposed for some bacteria that different enzymes involved in PG biosynthesis might act in concert or may form more active dimmer forms in vivo. Therefore the aim of this project is to study the interactions between penicillin binding proteins of Neisseria meningitidis and their functional organisation. The project will use a multidisciplinary approach applying bacteriological, molecular and biochemical methods as well as electron microscopy. The research should give a possibility to determine interactions between different PBPs of meningococci and to elucidate a role of different parts/domains of PBPs through the assessment of their influence on structural modification of N. meningitidis PG.
Champ scientifique
Appel à propositions
FP7-PEOPLE-ERG-2008
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Régime de financement
MC-ERG - European Re-integration Grants (ERG)Coordinateur
00 725 Warszawa
Pologne