Disease caused by Neisseria meningitidis (Nm), remains a serious public health problem worldwide. The molecular mechanisms underlying the pathogenesis of meningococcal meningitis are not fully understood. We addressed this problem by the discovery and investigation of new genes present in Nm but absent from the closely-related gonococcus (N. gonorrhoeae), which does not cause meningitis. Such genes may therefore define the differential pathogenicity of meningococcal disease. Using a genomic subtraction technique we isolated probes for genes which were present in Nm, but absent from N. gonorrhoeae. These genetic differences were found to be grouped in three distinct regions of the chromosome, one of which (about 20 kb in extent) was common to all the strains tested. Aims of the Project This project will investigate this common, Nm-specific region genetically and with respect to the virulence of the meningococcus. This will be achieved by sequencing and mutational analysis of the genes present in this region of DNA.
Expected Benefits The information will lead to an understanding of the biological significance of this region of the meningococcal chromosome, and may shed light generally on the pathogenesis of meningitis and the crossing of the blood-brain barrier by bacterial pathogens.