Neisseria meningitidis is a leading cause of meningitis and septicemia worldwide, associated with a high mortality rate. Since the increasing number of culture negative cases has been observed, and an immediate initiation of proper antibiotic therapy is crucial for favourable outcomes, there is an urgent need to develop rapid and specific non-culture methods of predicting of meningococcal susceptibility to penicillin. Although penicillin remains the drug of choice in the treatment of invasive meningococcal disease (IMD), since the 1980s an increasing number of meningococci with reduced susceptibility to penicillin has emerged worldwide.
This phenotype is thought to be due to an alteration of penicillin binding proteins, involved in the late stages of peptidoglycan (PG) biosynthesis. Therefore the aim of this project is to develop molecular tools to predict the susceptibility of N. meningitidis to antibiotics and a pathophysiological analysis of the effects of altered meningococcal susceptibility to penicillin on virulence of the strain. This project will use a multidisciplinary approach applying bacteriological, molecular, biochemical and pathophysiological methods. A basic part of the research will be focused on the mechanisms of the diminished susceptibility to penicillin as well as on the structural modification in PG, to elucidate the role of PG modification in the meningococcal pathogenesis. In addition to gaining more knowledge in the field of IMD, the project is also very important from the public health perspective.
The development and then implementation of accessible molecular methods to predict meningococcal susceptibility to antibiotics should permit faster and thus improved management of meningococcal infections, with better epidemiological surveillance as well as the analysis of the impact of the decreased susceptibility to penicillin on meningococcal pathogenesis.
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