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Investigation of New Drugs that Inhibit Acquisition of Iron from Oral Environments in the Periodontopathogen Porphyromonas gingivalis.

Research Project

Project/Area Number 13557149
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Morphological basic dentistry
Research InstitutionNagasaki University

Principal Investigator

NAKAYAMA Koji  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (80150473)

Co-Investigator(Kenkyū-buntansha) TERAGUCHI Susumu  Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd., Section Chief, 栄養科学研究所・基礎研究室, 室長
SHIMOKAWA Osamu  Kyushu University, Graduate School of Dental Sciences, Lecturer, 大学院・歯学研究院, 講師 (40136502)
OHARA Naoya  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70223930)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2003: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsOral Anaerobic Bacteria / Porphyromonas gin givalis / Porphyrin / Lactoferrin / Iron Acquisition / ポルフィロモナス・ジンジハリス / ラクトフェリシン
Research Abstract

The oral anaerobic bacterium Porphyromonas gingivalis is implicated as an important pathogen for periodontitis. A non-iron metalloporphyrin, indium-protoporphyrin (In-PPIX) was examined for antibacterial effects on P. gingivalis. In-PPIX showed growth inhibition of P. gingivalis in a dose-dependent fashion. An ihtB mutant of p. gingivalis was more resistant to In-PPIX than the wild type parent, while an hmuR mutant was more sensitive, indicating that In-PPIX might be incorporated by the IhtB-mediated iron uptake pathway. An sod mutant of P. gingivalis showed almost the same sensitivity to In-PPIX, which was contrast with the finding that E. coil SOD-null mutant shows hypersensitive to galium-protoporphyrin. Moreover, P. gingivalis dps mutant showed more resistant to In-PPIX than the wild type parent, suggesting that Dps protein which is one of iron-containing proteins might be related with In-PPIX toxicity. We already found that lactoferrin and its active peptide domain, lactoferricin have the ability to inhibit growth of P. gingivalis. Lactoferrin removes the hemoglobin receptor protein (HbR) from the P. gingivalis cell surface with the result of growth inhibition. This inhibition system seems to be different from that of In-PPIX, suggesting that use of both chemicals may show a synergistic effect on growth of P. gingivalis.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Shoji, M. et al.: "The major structural components of two...."Molecular Microbilogy. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamaguchi, A. et al.: "Autolysis of Porphyromonas gingivalis is accompanied...."Microbiology and Immunology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goulet, V. et al.: "Cleavage of human transferrin by Porphyromonas...."Infection and Immunity. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inaba, H. et al.: "Effect of enamel matrix derivatives on periodontal...."Journal of Periodontology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, K. et al.: "Infection-induced up-regulation of the costimulatory...."Journal of Biological Chemistry. 279. 13555-13563 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamoto, M. et al.: "Inhibitory effect of green tea catechins on...."Oral Microbiology and Immunology. 19. 118-120 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shoji, M., Naito, M., Yukitake, H., Sato, K., Sakai, E., Ohara, N., Nakayama, K.: "The major structural components of two cell-surface filaments of Porphyromonas gingivalis are maturated through lipoprotein precursors"Mol.Microbiol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamaguchi,.A., Nakano, M., Shoji, M., Nakamura, R., Sagane, Y., Okamoto, M., Watanabe, T., Ohyama, T., Ohta, M., Nakayama, K.: "Autolysis of Porphyromonas gingivalis is accompnied by an increase in several periodontal pathogenic factors in the supernatant"Miicrobiol.Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goulet, V., Britigan, B., Nakayama, K., Grenier, D.: "Cleavage of human transferrin by Porphyromonas gingivalis gingipains promotes the formation of hydroxyl radicals"Infect.Immun.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inaba, H., Kawai, S., Nakayama, K., Okahashi, N., Amano, A.: "Effect of enamel matrix derivative on periodontal ligament cells diminished by Porphyromonas gingivalis."J.Periodontol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, K., Ohara, N., Hotokezaka, H., Fukumoto, S., Yuasa, K., Naito, M., Fujiwara, T., Nakayama, K.: "Infection-induced up-regulation of the costimulatory molecule 4-1BB in osteoblastic cells and its inhibitory effect on M-CSF/RANKL-induced in vitro osteoclastogenesis"Biol.Chem.. 279(14). 13555-13563 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamoto, M., Sugimoto, A., Leung, K.-, Nakayama, K., Kamaguchi, A., Maeda, N.: "Inhibitory effect of green tea catechins on cysteine proteinases in Porphyromonas gingivalis."Oral Microbiol.Immunol. 19. 118-120 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Grenier, D.et al.: "Effect of inactivation of the Arg- and/or Lys-gingipain Gene on Selected Virulence and Physiological Properties of Porphyromonas gingivalis"Infect.Immun.. 71. 4742-4748 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Houle, M-A.et al.: "The collagenolytic activity of Porphyromonas gingivalis is due to its Arg-gingipain"FEMS Microbiol.Lett.. 221・2. 181-185 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Houle et al.: "The collagenolytic activity of Porphyromonas gingivalis is..."FEMS Microbiology Letters. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawaguchi et al.: "Adhesins encoded by the gingipain genes of Porphyromonas..."Microbiology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueshima et al.: "Purification, gene cloning, gene expression and mutants..."Infection and Immunity. 71・3. 1170-1178 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中山浩次: "口腔偏性嫌気性細菌Porphyromonas gingivalisの病原性に関する分子遺伝学的研究(日本細菌学会平成12年度小林六造記念賞受賞論文)"日本細菌学雑誌. 56・4. 573-585 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Grenier, D. et al.: "Role gingipains in growh of Porphyromonas gingivalis in the presence of human seram albumin"Infection and Immunity. 69・8. 5166-5172 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamaguchi, A. et al.: "Coaggregation of Porphyromonas gingivalis and Prevotella intermedia"Microbiology and Immunology. 44・9. 649-656 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chen, T. et al.: "Porphyromonas gingivalis gingipains and odhesion to epithelial cells"Infection and Immunity. 69・5. 3048-3056 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Grenier, D. et al.: "Studies in the aminopeptidace activities of Porphyromonas gingivalis"Oral Microbiology and Immunology. 16・4. 212-217 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoneda, M. et al.: "Mixed infection of Porphyromonas gingivalis and Bacteroides for sythus in a murine adscess model : involvemanl of gingipains in a synergistic effect"J.Pariadontal Research. 36. 237-243 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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