Elucidation of the relationship between P. gulae infection and periodontitis onset mechanism

• Project/Area Number: 17K11612
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Okayama University
• Principal Investigator: Inaba Hiroaki 岡山大学, 医歯薬学総合研究科, 准教授 (70359850)
• Co-Investigator(Kenkyū-buntansha): 仲野 道代 (松本道代) 岡山大学, 医歯薬学総合研究科, 教授 (30359848)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: P. gulae / 付着侵入 / 歯肉上皮細胞 / インテグリン / 歯周病 / Porphyromonas gulae / 線毛

Outline of Final Research Achievements

P. gulae type C and some type B strains invaded gingival epithelial cells at significantly greater levels than the other strains, at the same level of efficiency as P. gingivalis with type II fimbriae. Adhesion and invasion of
gingival epithelial cells by P. gulae were inhibited by cytochalasin D and sodium azide, indicating the requirements of actin polymerization and energy metabolism for those activities. Invasion within gingival epithelial cells was blocked by staurosporine, while nocodazole and　cycloheximide had negligible　effects on either adhesion or invasion. P. gulae proteases were found to be essential for　adhesion and invasion of gingival epithelial cells, while its DNA and RNA, and protein synthesis were unnecessary for those activities. Additionally, α5β1 integrin antibodies significantly inhibited adhesion and invasion by P. gulae. This is the first report to characterize P. gulae adhesion and invasion of human gingival epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

人畜共通感染症の可能性をもつP. gulae 感染による歯周病発症の解明は、今後増加が予想される動物由来歯周病菌による感染症に対する創薬、予防方法や治療方法の開発、医療関係者や患者への教育内容充実が十分考えられることができる。本研究課題により解明したP. gulae感染による歯周病発症との関連性は、特に、伴侶動物を飼育する歯周病患者のクオリティー・オブ・ライフ維持へとつなげるためへのテーゼとなり、社会的意義も非常に高いと考えられる。

Research Products

• [Int'l Joint Research] University of Louisville(米国)
• [Int'l Joint Research] University of Louisville(米国)
• [Journal Article] Inhibition of Porphyromonas gulae and periodontal disease in dogs by a combination of clindamycin and interferon alpha (2020)
  • Author(s): Nomura, R.*, Inaba, H.*, Yasuda, H.*, Shirai, M., Kato, Y., Murakami, M., Iwashita, N., Shirahata, S., Yoshida, S., Matayoshi, S., Yasuda, J., Arai, N., Asai, F., Matsumoto-Nakano, M., Nakano, K. (*contributed equally to authors)
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 3113-3113
  • DOI: 10.1038/s41598-020-59730-9
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory effect of a mouth rinse formulated with chlorhexidine gluconate, ethanol, and green tea extract against major oral bacterial species (2020)
  • Author(s): Nomura, R., Inaba, H., Matayoshi, S., Yoshida, S., Matsumi, Y., Matsumoto-Nakano, M., Nakano, K
  • Journal Title: Journal of Oral Science Volume: 62 Issue: 2 Pages: 206-211
  • DOI: 10.2334/josnusd.18-0483
  • NAID: 130007821416
  • ISSN: 1343-4934, 1880-4926
  • Peer Reviewed / Open Access
• [Journal Article] Adhesion and invasion of gingival epithelial cells by Porphyromonas gulae (2019)
  • Author(s): Hiroaki Inaba, Ryota Nomura, Yukio Kato, Hiroki Takeuchi, Atsuo Amano, Fumitoshi Asai, Kazuhiko Nakano, Richard J. Lamont, Michiyo Matsumoto-Nakano
  • Journal Title: PLOS one Volume: 14 Issue: 3 Pages: e0213309-e0213309
  • DOI: 10.1371/journal.pone.0213309
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification and molecular characterization of Porphyromonas gulae fimA types among cat isolates. (2019)
  • Author(s): Naoki Iwashita, Ryota Nomura, Mitsuyuki Shirai, Yukio Kato, Masaru Murakami, Saaya Matayoshi, Tamami Kadota, So Shirahata, Leo Ohzeki, Nobuaki Arai, Junya Yasuda, Hidemi Yasuda, Hiroaki Inaba, Michiyo Matsumoto-Nakano, Kazuhiko Nakano, Fumitoshi Asai.
  • Journal Title: Veterinary Microbiology Volume: 229 Pages: 100-109
  • DOI: 10.1016/j.vetmic.2018.12.018
  • Peer Reviewed
• [Journal Article] Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients. (2018)
  • Author(s): Misaki T, Naka S, Wato K, Hatakeyama R, Nagasawa Y, Ito S, Inaba H, Nomura R, Matsumoto-Nakano M, Nakano K
  • Journal Title: Nephron Volume: Epub Issue: 2 Pages: 143-149
  • DOI: 10.1159/000487103
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cell cycle arrest and apoptosis induced by Porphyromonas gingivalis requires JNK- and p53-mediated p38 activation in human trophoblasts (2018)
  • Author(s): Hiroaki Inaba, Atsuo Amano, Richard J. Lamont, Yukitaka Murakami, Michiyo Matsumoto-Nakano.
  • Journal Title: Infection and Immunity Volume: in press Issue: 4
  • DOI: 10.1128/iai.00923-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Characterization of bacterial proteases from Porphyromonas gulae strains (2020)
  • Author(s): Urmi Saki Alam, Inaba, H., Yoshida, S., Nomura, R., Nakano, K., Matsumoto-Nakano, M
  • Organizer: 第93回日本細菌学会
• [Presentation] 岡山大学病院外来歯科領域における経口第三世代セフェム経口抗菌薬の使用量の削減について (2020)
  • Author(s): 東恩納司、岡崎昌利、稲葉裕明、飯尾耕治、筧彩佳、宮村純子、草野展周、塚原宏一
  • Organizer: 第35回日本環境感染学会
• [Presentation] VREのアウトブレイク事例とその解析 (2020)
  • Author(s): 筧彩佳、宮村純子、飯尾耕治、東恩納司、岡崎昌利、稲葉裕明、草野展周、塚原宏一
  • Organizer: 第35回日本環境感染学会
• [Presentation] 動物由来歯周病原菌のプロテアーゼ活性の評価 (2019)
  • Author(s): 吉田翔、稲葉裕明、Urmi Saki Alam、野村良太、仲野和彦、仲野道代
  • Organizer: 第40回岡山歯学会総会ならびに学術集会
• [Presentation] サイクロデキストランがStreptococcus mutansのバイオフィルム形成に与える影響 (2019)
  • Author(s): 浅海春華、松三友紀、髙島由紀子、仲周平、稲葉裕明、仲野道代
  • Organizer: 第40回岡山歯学会総会ならびに学術集会
• [Presentation] Porphyromonas gulae 由来のプロテアーゼ活性の評価 (2019)
  • Author(s): 吉田翔、稲葉裕明、Urmi Saki Alam、野村良太、仲野和彦、仲野道代
  • Organizer: 第38回日本小児歯科学会中四国地方会大会
• [Presentation] Porphyromonas gulae LPSによるTLR2／TLR4 を介した免疫応答制御の解明 (2019)
  • Author(s): 稲葉裕明、吉田翔、仲野道代
  • Organizer: 第61回歯科基礎医学会総会
• [Presentation] コンクールFとその構成物質における口腔細菌種への増殖抑制効果の検討 (2019)
  • Author(s): 又吉紗綾、野村良太、稲葉裕明、吉田 翔、松三友紀、仲野道代、仲野和彦
  • Organizer: 第57回日本小児歯科学会
• [Presentation] TLR2/TLR4 controls Porphyromonas gulae LPS- induced inflammatory responses in Ca9-22 cells (2019)
  • Author(s): Yoshida, S., Inaba, H., Nomura, R., Nakano, K., Matsumoto-Nakano M
  • Organizer: 97th IADR
  • Int'l Joint Research
• [Presentation] Streptococcus mutans transiently induces IgA nephropathy-like lesion in rats (2019)
  • Author(s): Wato, K.,, Naka, S., Misaki, T., Nagasawa, Y., Ito, S., Inaba, H., Nomura, R. Matsumoto-Nakano M., Nakano, K
  • Organizer: 97th IADR
  • Int'l Joint Research
• [Presentation] Porphyromonas gulaeの歯肉上皮細胞株への付着・侵入機構の解析 (2018)
  • Author(s): 稲葉裕明、野村良太、仲野和彦、仲野道代
  • Organizer: 第９１回日本細菌学会
• [Presentation] Porphyromonas gulae LPS による歯肉上皮細胞の炎症性反応の評価 (2018)
  • Author(s): 吉田翔、稲葉裕明、Urmi Saki Alam、野村良太、仲野和彦、仲野道代
  • Organizer: 第５６回日本小児歯科学会
• [Presentation] Porphyromonas gulaeが産生するプロテアーゼに関する検討 (2018)
  • Author(s): Urmi Saki Alam、吉田翔、稲葉裕明、野村良太、仲野和彦、仲野道代
  • Organizer: 第５６回日本小児歯科学会
• [Presentation] 乳酸菌由来のバクテリオシンがStreptococcus mutansのバイオフィルム形成に与える影響 (2018)
  • Author(s): 森本節代、森川優子、高島由紀子、仲周平、稲葉裕明、仲野道代
  • Organizer: 第５６回日本小児歯科学会
• [Presentation] 生体機能性材料S-PRGフィラーが口腔バイオフィルム形成に与える影響 (2018)
  • Author(s): 高島由紀子、森川優子、森本節代、稲葉裕明、仲野道代
  • Organizer: 第５６回日本小児歯科学会
• [Presentation] 歯周病原性菌C. rectus と齲蝕原性菌cnm遺伝子陽性S. mutansの口腔内の存在はIgA腎症患者の蛋白尿と関連する (2018)
  • Author(s): 三﨑太郎、塩岡天平、千葉圭、小野雅史、鈴木由美子、磯﨑泰介、仲 周平、和唐薫子、畠山理那、長澤康行、伊藤誓悟、稲葉裕明、野村良太、仲野道代、仲野和彦
  • Organizer: 第６１回日本腎臓学会学術総会
• [Presentation] Presence of Streptococcus mutans with collagen-binding protein is associated with the onset of IgA nephropathy and proteinuria in these patients (2018)
  • Author(s): 伊藤誓悟、三﨑太郎、野村良太、山形瑛、松原秀史、今給黎敏彦、大島直紀、仲 周平、和唐薫子、畠山理那、長澤康行、稲葉裕明、仲野道代、仲野和彦、熊谷裕生
  • Organizer: 第６１回日本腎臓学会学術総会
• [Presentation] Porphyromonas gulae線毛の遺伝子多型と歯肉上皮細胞への侵入能 (2018)
  • Author(s): 稲葉裕明、吉田翔、仲野道代
  • Organizer: 第６０回歯科基礎医学会総会
• [Presentation] 生体機能材料S-PRGフィラーが口腔バイオフィルムに与える影響 (2018)
  • Author(s): 森川優子、高島由紀子、仲周平、稲葉裕明、仲野道代
  • Organizer: 第３９回岡山歯学会総会ならびに学術集会
• [Presentation] 造血幹細胞移植施行患者における口腔レンサ球菌の分布 (2018)
  • Author(s): 森川優子、吉田衣里、角田陽子、高島由紀子、平野慶子、仲周平、稲葉裕明、仲野道代
  • Organizer: 第３７回日本小児歯科学会中四国地方会大会
• [Presentation] Porphyromonas gulae LPS activates inflammatory responses in gingival epithelial cells (2018)
  • Author(s): Sho Yoshida, Hiroaki Inaba, Ryota Nomura, Kazuhiko Nakano, Michiyo Matsumoto-Nakano
  • Organizer: 第６６回国際歯科研究学会日本部会
  • Int'l Joint Research
• [Presentation] Intravenous Administration of Streptococcus mutans Induces IgA Nephropathy in Rats (2018)
  • Author(s): Kaoruko. Wato, Syuhei Naka, Taro Misaki, Rina Hatakeyama, Yasuyuki Nagasawa, Seigo Ito, Hiroaki Inaba, Ryota Nomura, Michiyo Matsumoto-Nakano, Kazuhiko Nakano
  • Organizer: 第６６回国際歯科研究学会日本部会
  • Int'l Joint Research
• [Presentation] 歯周病菌Porphyromonas gulae線毛遺伝子多型とヒト歯肉上皮細胞への付着・侵入能の解析 (2017)
  • Author(s): 吉田翔、稲葉裕明、野村良太、仲野和彦、仲野道代
  • Organizer: 第５５回 日本小児歯科学会大会
• [Presentation] カイコ感染モデルを用いたPorphyromonas gulae FimA の病原性解析 (2017)
  • Author(s): 吉田翔、稲葉裕明、仲野道代
  • Organizer: 第５９回 歯科基礎医学会学術大会
• [Presentation] Campylobacter rectus and cnm-positive Streptococcus mutans strains harbored in oral cavity increase urinary protein in IgAN patients (2017)
  • Author(s): Kaoruko. Wato, Syuhei Naka, Taro Misaki, Rina Hatakeyama, Yasuyuki Nagasawa, Seigo Ito, Hiroaki Inaba, Ryota Nomura, Michiyo Matsumoto-Nakano, Kazuhiko Nakano
  • Organizer: 65th JADR
  • Int'l Joint Research
• [Presentation] 乳酸菌が産生するバクテリオシンが口腔バイオフィルム形成に与える影響 (2017)
  • Author(s): 森本節代、森川優子、髙島由紀子、仲周平、稲葉裕明、仲野道代
  • Organizer: 第３６回日本小児歯科学会中四国地方会大会