2003 Fiscal Year Final Research Report Summary
Investigation of New Drugs that Inhibit Acquisition of Iron from Oral Environments in the Periodontopathogen Porphyromonas gingivalis.
Project/Area Number |
13557149
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Morphological basic dentistry
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Research Institution | Nagasaki 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)
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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)
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Project Period (FY) |
2001 – 2003
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Keywords | Oral Anaerobic Bacteria / Porphyromonas gin givalis / Porphyrin / Lactoferrin / Iron Acquisition |
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.
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[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).
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「研究成果報告書概要(欧文)」より
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[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).
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より