| Project/Area Number | 08407059 |
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YAMAMOTO Kenji KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY PROFESSOR, 歯学部, 教授 (40091326)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKUBA Takayuki KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY ASSISTANT PROFESSOR, 歯学部, 助手 (30264055)
NAKANISHI Hiroshi KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY ASSISTANT PROFESSOR, 歯学部, 助手 (20155774)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed(Fiscal Year 1998)
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| Budget Amount *help |
¥9,400,000 (Direct Cost : ¥9,400,000)
Fiscal Year 1998 : ¥4,500,000 (Direct Cost : ¥4,500,000)
Fiscal Year 1997 : ¥4,900,000 (Direct Cost : ¥4,900,000)
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| Keywords | Porphyromonas gingivalis / oral anaerobic bacterium / virulence factors / Arg-gingipain / Lys-gingipain / crysteine proteinase / periodontal disease / Porphyromonas gingivalis / 病原性プロテアーゼ / 病原性発現機序 / 病原菌プロテアーゼ / カテプシン |
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| Research Abstract |
The oral anaerobic bacterium Porphyromanas gingivalis has been implicated as a major etiologic agent of progressive periodontal disease. This bacterium produces a novel class of cysteine proteinases, now termed Arg-gingipain (RGP) and Lys-gingipain (KGP), that are responsible for the trypsine-like activity. In order to determine whether RGP and KGP are important for pathophysiology of the organism we have constructed RGP- and KGP-deficient mutants. The RGP-null mutant almost completely lost the inhibitory effect on chemiluminescence response of PMNs stimulated by serum-activated zymosan, suggesting that RGP is responsible for disruption of the bactericidal function of PMNs by P.gingivalis. The RGP-null mutant also showed a greater decrease of hemagglutination observed with the wild-type strain, suggesting that the rgp genes are involved in the hemagglutination activity of this organism. In addition, the RGP-null mutant showed little or no fimbriation. Since the precursors of fimbrilin and a 75-kDa protein underwent abnormal processing, RGP was shown to make a significant contribution to the virulence of P.gingivalis through processing of these cell surface proteins. On the other hand, the KGP-null mutant showed a greater decrease of the hemagglutination activity, but it retained the strong ability to disrupt the bactericidal activity of PMNs. More important, the KGP-null mutant-did not form black-pigmented colonies on blood agar plates, indicating its defect of hemoglobin adsorption and heme accumulation. These results strongly suggest that both RGP and KGP make a great contribution to the virulence of P.gingivalis through common and different mechanisms.
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