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Nationwide prospective study on community-acquired bacterial meningitis: from genetics to therapy (MeninGene)
Date du début: 1 févr. 2012, Date de fin: 31 janv. 2017 PROJET  TERMINÉ 

Meningitis is an inflammation of the membranes covering the brain and spinal cord (the meninges). Each year 35,000 European patients suffer from bacterial meningitis, resulting in 7000 deaths and leaving 7000 disabled. Streptococcus pneumoniae and Neisseria meningitidis are the most common causative bacteria of bacterial meningitis. These bacteria are common colonizers, but in some individuals, they are able to spread to the bloodstream, slip through the blood-brain barrier and cause meningitis, with devastating consequences. Genetics of host and pathogen are considered crucial in this host-pathogen interaction. Our objectives are to identify and characterize host genetic traits and bacterial virulence factors controlling occurrence and outcome of bacterial meningitis. In a nationwide prospective cohort study, using pathway and total exome sequencing, we will search for genetic variants in 2000 patients with community-acquired bacterial meningitis and 2000 controls. On the pathogen side, using whole genome sequencing, we will systematically search for new bacterial virulence factors in the 2000 causative bacteria. Subsequently, by analyzing clinical data, serum and cerebrospinal fluid, we will examine the potential impact and functionality of these host and pathogen factors. Next, we will validate and explore our findings in an animal model of meningitis and investigate whether treatment against these specific components can improve outcome. Finally, we will initiate an open-access European database on the genetics in bacterial meningitis. In addressing our objectives, I will combine my expertise in bacterial meningitis with groundbreaking, translational approaches using clinical data, human samples, next generation sequencing, in vitro techniques, and a mouse model. The results of this project will be translated into novel therapeutic strategies to advance patient care and will also be important for the development of disease prevention and vaccines.