Comparative genomic analysis, and host-pathogen interactions of Porphyromonas gingivalis

It is estimated that 30% of American adults are affected by chronic periodontitis, which is an inflammatory disease that destroys the gums and supporting structures of the teeth. Porphyromonas gingivalis is a gram-negative obligate anaerobe, which has been strongly implicated in the etiology of the disease.; Previous research has led to conflicting answers with respect to the amount of genetic variability that exists within the species. In previous studies we used heteroduplex analysis of the intergenic spacer region between the 16s and 23s rRNA genes, to type P. gingivalis strains in human plaque samples, and sequence analysis of the same region to determine the relatedness of strains to one another. The results from these studies suggest that there is a correlation between ISR sequence phylogeny, and the disease-associated phenotype of the strains. The goals of the study described in chapter 2 were to more comprehensively examine the genomic variability among strains of P. gingivalis, and to determine the relatedness of the strains to one another based on genome content. Whole genome microarray analysis was performed to compare the genomic content of 7 clinically prevalent P. gingivalis strains. 133 genes that were modified in at least one of the test strains relative to strain W83 were identified. Phylogenetic reconstruction based on the microarray results revealed that ISR sequence phylogeny and genome content phylogeny predict similar relationships among P. gingivalis strains, and that there is a strong correlation between the genomic content and disease-associated phenotype of P. gingivalis strains.; The studies presented in chapters 3 and 4 focused on the development and use of a Drosophila melanogaster killing model to characterize P. gingivalis-host interactions. We demonstrate that P. gingivalis can kill Drosophila, and that differences in virulence among P. gingivalis strains can be observed in the Drosophila killing model. We also demonstrate that several P. gingivalis components that are important for pathogenesis in mammalian systems are also important for pathogenesis in the Drosophila model. Finally we identify several host components that are involved in the immune response to P. gingivalis infection, using mutant Drosophila lines.