Gain and loss of the gonococcal genetic island in Neisseria

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DESCRIPTION (provided by applicant): The gonococcal genetic island (GGI) is a 57 kb region of DNA that is found in the chromosomes of 80% of Neisseria gonorrhoeae strains and was recently identified in Neisseria meningitidis. The GGI sequence shows evidence that it was horizontally acquired from another bacterial species. It is flanked by a 23-bp repeat, one copy of which makes up most of the dif site at the gonococcal replication terminus. The second copy of the repeat is part of an imperfect copy of the dif sequence. dif is a sequence that is recognized by the site-specific recombinase XerCD. In E. coli it has been shown that dif and XerCD facilitate the resolution of chromosomal dimers that result from homologous recombination following chromosomal replication. The identification of the GGI in N. meningitidis suggests that the GGI may be horizontally transferred between Neisseria species. This proposal describes experiments to characterize the mechanisms involved in acquisition and excision of the GGI and the phenotypes associated with acquisition of the GGI by N. meningitidis strains. Characterization of GGI loss in N. gonorrhoeae indicates that the dif sequence facilitates excision by site-specific recombination. Limited DNA sequence information on the GGI from several N. meningitidis isolates identifies type IV secretion system genes in the meningococcal isolates, but that certain putative surface components exist in variant forms. These data suggest that the type IV secretion system may function differently in N. meningitidis and may be subject to immune surveillance. These studies will further characterize the gene content of the N. meningitidis GGIs and examine their effects on infection of human cells in culture. This proposal describes experiments to characterize the mechanisms involved in acquisition and excision of the GGI and the phenotypes associated with acquisition of the GGI by N. meningitidis strains. These studies will further characterize the gene content of the N. meningitidis GGIs and examine their effects on infection of human cells in culture.