Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae

The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cau se dramatically different diseases despite strong relatedness at the geneti c and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. go norrhoeae. We previously used subtractive hybridization to identify DNA seq uences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N . gonorrhoeae. In this report we show that these sequences mark eight genet ic islands that range in size from 1.8 to 40 kb and whose chromosomal locat ion is constant. Five of these genetic islands were conserved within a repr esentative set of strains and/or carried genes with homologies to known vir ulence. factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy iden tified one island, region 8, which is needed to induce bacteremia in an inf ant rat model of meningococcal infection. Region 8 encodes a putative sider ophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neithe r were the mutant strains altered in their ability to interact with endothe lial cells, suggesting that such interactions are not encoded by large gene tic islands in N. meningitidis.