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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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University of Michigan Ann Arbor
Schools of Dentistry
Ann Arbor
United States
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Sweier, Domenica G; Shelburne, P Sandra; Giannobile, William V et al. (2009) Immunoglobulin G (IgG) class, but Not IgA or IgM, antibodies to peptides of the Porphyromonas gingivalis chaperone HtpG predict health in subjects with periodontitis by a fluorescence enzyme-linked immunosorbent assay. Clin Vaccine Immunol 16:1766-73
Shelburne, Charles E; Shelburne, P Sandra; Dhople, Vishnu M et al. (2008) Serum antibodies to Porphyromonas gingivalis chaperone HtpG predict health in periodontitis susceptible patients. PLoS One 3:e1984
Shelburne, Charles E; Coopamah, Malini D; Sweier, Domenica G et al. (2007) HtpG, the Porphyromonas gingivalis HSP-90 homologue, induces the chemokine CXCL8 in human monocytic and microvascular vein endothelial cells. Cell Microbiol 9:1611-9
Shelburne, Charles E; An, Florence Y; Dholpe, Vishnu et al. (2007) The spectrum of antimicrobial activity of the bacteriocin subtilosin A. J Antimicrob Chemother 59:297-300
Kozarov, Emil; Sweier, Domenica; Shelburne, Charles et al. (2006) Detection of bacterial DNA in atheromatous plaques by quantitative PCR. Microbes Infect 8:687-93
Dhople, Vishnu; Krukemeyer, Amy; Ramamoorthy, Ayyalusamy (2006) The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim Biophys Acta 1758:1499-512
Ramamoorthy, Ayyalusamy; Thennarasu, Sathiah; Tan, Anmin et al. (2006) Deletion of all cysteines in tachyplesin I abolishes hemolytic activity and retains antimicrobial activity and lipopolysaccharide selective binding. Biochemistry 45:6529-40
Shelburne, Charles E; Coulter, Wilson A; Olguin, De'avlin et al. (2005) Induction of {beta}-defensin resistance in the oral anaerobe Porphyromonas gingivalis. Antimicrob Agents Chemother 49:183-7
Kozarov, Emil V; Dorn, Brian R; Shelburne, Charles E et al. (2005) Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler Thromb Vasc Biol 25:e17-8
Shelburne, C E; Gleason, R M; Coulter, W A et al. (2005) Differential display analysis of Porphyromonas gingivalis gene activation response to heat and oxidative stress. Oral Microbiol Immunol 20:233-8

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