<italic>Porphyromonas gingivalis</italic> Hsp90 recognition in periodontal disease.
Sweier, Domenica G.
2004
Abstract
We reported that elevated levels of serum antibody to Hsp90 stress protein in individuals colonized with <italic>Porphyromonas gingivalis</italic> were associated with periodontal health. We also identified a <italic>P. gingivalis </italic> Hsp90 homologue (HtpG) that cross-reacts with human Hsp90 and appears to be localized to membrane fractions. <italic>P. gingivalis</italic> has been implicated in the etiology of Chronic Periodontal Disease which is a treatment challenge for dentistry. Additionally, associations between microbial virulence and stress protein expression have been identified in important human infections. This thesis describes the studies addressing the following hypothesis: <italic>Specific epitopes of the Porphyromonas gingivalis Hsp90 homologue are putative virulence determinants that may be blocked by antibodies in sera of healthy subjects</italic>. We have (i) cloned and characterized the <italic>P. gingivalis htpG</italic> gene and protein, (ii) created a <italic>P. gingivalis htpG</italic> disruption mutant and looked at growth, adherence and invasion into human cells, (iii) generated polyclonal rabbit anti-<italic>P. gingivalis</italic> recombinant HtpG (<italic>Pg</italic> rHtpG) antiserum, and (iv) mapped the immunogenic regions of the <italic> P. gingivalis</italic> HtpG dominant in recognition in human health and periodontal disease. The <italic>P. gingivalis</italic> ATCC 33277 <italic>htpG</italic> sequence has Genbank accession number AF176245. The translated HtpG is 684 amino acids and contains a unique C-terminal insert of 65 amino acids not found in other HtpGs/Hsp90s sequenced to date. The <italic>P. gingivalis htpG</italic> disruption mutant does not appear to affect growth at optimal conditions, and there is no difference in adherence and invasion compared to the wild type onto/into human epithelial cells. I identified immunoreactive regions of the <italic>P. gingivalis</italic> HtpG using rabbit anti-<italic>Pg</italic> rHtpG and human serum with a fusion protein library consisting of <italic>Pg</italic> HtpG peptides linearly representative of the <italic>Pg</italic> HtpG. Healthy human serum showed a trend of higher anti-<italic>Pg</italic> HtpG peptide titer compared to Chronic Periodontal Disease. Statistically significant differences exist between healthy serum and Aggressive Periodontal Disease when measuring anti-<italic>Pg</italic> HtpG and anti-<italic>Pg</italic> HtpG peptides. My work, in conjunction with ongoing studies in our laboratory, suggests a modulatory mechanism mediated by <italic>P. gingivalis</italic> HtpG which suppresses the proinflammatory cytokine response and is attenuated by the presence of epitope-specific anti-Hsp90 antibodies.Subjects
Hsp90 Periodontal Disease Porphyromonas Gingivalis Recognition
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