PTS-mediated virulence regulation in Neisseria meningitidis

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Neisseria meningitidis, the causative agent of meningitis, is a pathogen constantly present in the nasopharynx of a large part of any human population (in Europe between 5 and 20%). For reasons barely understood, it occasionally enters the blood stream and can even cross the brain-blood barrier, thereby causing severe infections. Despite antibiotic treatment, 10% of the severe infections have a fatal outcome. Mutations affecting certain PTS components (hprK and ptsff) have been shown to diminish the virulence of N. meningitidis. In response to the carbon metabolic state of bacteria, PTS proteins in the cells are more or less phosphorylated. Because N. meningitidis encounters quite different concentrations of glucose in the various tissues it can colonise, the PTS-mediated signal is thought to be important for the adhesion to epithelial and endothelial cells. The effect of the PTS proteins is likely to be mediated via YhbJ and the sigma factor RpoN. Protein/protein interaction studies will confirm or refute this hypothesis. Transcriptome and proteome analyses of mutants affected in PTS proteins and exhibiting a diminished virulence are expected to allow the identification of the complete signal transduction pathway underlying the carbon metabolism-dependent control of N. meningitidis virulence. A detailed understanding of this signal transduction pathway is expected to allow in the long term the development of new antimicrobial agents affecting PTS proteins, which occur exclusively in bacteria.