Microorganisms produce new proteins during the infectious process. Expression of many of these proteins represents the response to stresses imposed by the host (stress-proteins, HSP) and is important to the microorganism's ability to pursue the infectious process. Defense of the host is often dependent on immunologic recognition of these proteins. Preliminary data presented in this application shows that humoral immunity to one such protein, HSP90, is associated with both gingival health and low level colonization by Porphyromonas gingivalis, one of the principal periodontal pathogens. There is a paucity of data on the stress proteins of the periodontal pathogens. The stress proteins are immunodominant and important antigens in other non-oral bacterial infections. Investigations of the stress proteins of periodontal pathogens may be crucial to our understanding of the etiology of periodontal disease. The long-term goals of this laboratory are to define the role(s) of stress proteins in the periodontal disease process by investigating their expression, regulation and interaction with host defense mechanisms. The first step, as outlined in this proposal, is to characterize the 90 kD stress protein of P. gingivalis which, based on our preliminary studies, is important in the organism's role in periodontal disease. The specific hypothesis to be tested in this proposal is: HSP90 is expressed by P. gingivalis during conditions that mimic the infectious process. Express of HSP90 by P. gingivalis contributes to its virulence and antibodies directed against P. gingivalis HSP90 are protective. We propose to test this hypothesis by: (1) characterizing the conditions under which P. gingivalis HSP90 is expressed; (2) cloning and sequencing the P. gingivalis HSP90 gene; (3) performing immuno electronmicroscopic studies to localize the HSP90 protein on the surface and inside the P. gingivalis cell; (4) evaluating the contribution HSP90 to the virulence of P. gingivalis in two animal models.
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