Periodontal diseases are one of the most common bacterial infections in developed countries. Although the identities of the bacteria responsible for the disease and the mechanisms of pathogenicity are understood to some degree, further insights into the molecular and cellular interactions between the pathogenic bacteria and the host are required before the disease can he brought under control. In this study, the interactions between Porphyromonas gingivalis, a periodontal pathogen, and gingival epithelial cells will be investigated. It has been established that P. gingivalis can invade primary cultures of gingival epithelial cells. The ultrastructural and biochemical requirements of P. gingivalis and of gingival epithelial cells that are necessary for invasion will be determined. A variety of inhibitors of epithelial cell functions, such as microfilament and microtubule formation, protein synthesis and energy metabolism, will be examined for their ability to inhibit the invasion process. Similarly, inhibitors of bacterial cell functions such as macromolecule synthesis and energy metabolism will be tested for their effects on invasion. Thus, the nature of the invasion process will be elucidated. The molecules of P. gingivalis that mediate adherence and induction of the invasion process will also be investigated. Surface molecules of P. gingivalis will be purified and examined for binding to epithelial cells. The genes for interactive molecules will be identified by cloning and transposon mutagenesis experiments. Finally, the physiology of the signal transduction, in particular calcium ion fluxes, that occurs in the epithelial cells subsequent to the initial interaction with P. gingivalis will be investigated. The information provided by these studies will enhance our understanding of how pathogenic bacteria and host cells interact during the disease process, thus facilitating the development of novel methods to control the disease.
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