Role of bacteriophage in Neisseria gonorrhoeae biology

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DESCRIPTION (provided by applicant): Neisseria gonorrhoeae contains 9 genetic islands that encode for bacteriophage. The role that these bacteriophage play in gonococcal biology is unknown. Bioinformatic analysis indicates that these islands are highly conserved in all gonococcal strains and absent in most commensal Neisseria. Transcriptome analysis indicates that regulation of their expression occurs, and that many bacteriophage genes are upregulated when grown under conditions that would mimic in vivo growth conditions (Low oxygen or iron, or under stress). The goal of this proposal is to decipher how bacteriophage encoded genes contribute to gonococcal biology. Since some of the phage encoded proteins have significant homology with proteins that are known to disrupt tight junctions, we have hypothesized that these genes enhance the invasive capacity of gonococci. The hypothesis that we will be testing is that the expression of specific bacteriophage encoded-genes allow the gonococcus to invade into tissues by a paracellular route of invasion. To test this hypothesis, we will construct variou deletion mutants, generating a panel of strains that are deficient in one or more gonococcal phage genomes/genes and test these mutants for their ability to invade into and cross between polarized epithelial cells. PUBLIC HEALTH RELEVANCE: Bacteriophage have been known to contribute to a variety of diseases. While it has been known for a long time that most pathogenic Neisseria strains contain numerous genetic islands that appear to be lysogens from temperate and filamentous bacteriophages, it wasn't until recent bioinformatic and transcriptome analysis that there was enough data to suggest that these phage could impact on virulence in neisserial biology. This project is designed to determine what role, if any, these phage play in gonococcal biology.