Comprehensive analysis of cariogenic bacteria cell surface proteins for risk of infective endocarditis

• Project/Area Number: 18K09831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Nomura Ryota 大阪大学, 歯学研究科, 准教授 (90437385)
• Co-Investigator(Kenkyū-buntansha): 鋸屋 侑布子 大阪大学, 歯学研究科, 助教 (40803078) ; 大継 將寿 大阪大学, 歯学研究科, 助教 (40803086)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: Streptococcus mutans / 感染性心内膜炎 / コラーゲン結合タンパク / う蝕 / 血管内皮細胞 / 血清 / IV型コラーゲン / RhoファミリーGタンパク質 / 細胞外マトリックス / 低分子量Gタンパク質 / ARHGEF38 / 齲蝕 / 菌体表層タンパク / う蝕病原性細菌 / 病原遺伝子 / 臨床検体

Outline of Final Research Achievements

We evaluated the pathogenicity of Streptococcus mutans for infective endocarditis using an animal model and cell culture experiments, with focus on 120-kDa collagen-binding proteins (CBP) on the surface of bacterial cells. S. mutans organisms were isolated from heart valve specimens extirpated from rats with both severe dental caries and heart valve injury, which led to occurrence of mild infective endocarditis. In addition, CBP-positive S. mutans-bound type IV collagen was found to induce cytoskeletal rearrangement of vascular endothelial cells and bacterial internalization.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、心疾患を有し口腔内にCBP 陽性のS. mutansが存在する場合には、重度のう蝕病変を放置することにより軽度の感染性心内膜炎を生じる可能性があることが示された。また、CBP 陽性のS. mutansは血管内皮細胞の表層に付着するだけでなく、細胞内にまで侵入して心臓弁に定着する可能性があることが明らかになった。本研究で得られた成果から、感染性心内膜炎の発症を防ぐために、心疾患を有する対象におけるう蝕の予防や早期治療の重要性が示唆された。

Research Products

• [Journal Article] Potential involvement of Streptococcus mutans possessing collagen binding protein Cnm in infective endocarditis (2020)
  • Author(s): Nomura Ryota、Otsugu Masatoshi、Hamada Masakazu、Matayoshi Saaya、Teramoto Noboru、Iwashita Naoki、Naka Shuhei、Matsumoto-Nakano Michiyo、Nakano Kazuhiko
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 19118-19118
  • DOI: 10.1038/s41598-020-75933-6
  • Peer Reviewed / Open Access
• [Journal Article] Contribution of severe dental caries induced by Streptococcus mutans to the pathogenicity of infective endocarditis (2020)
  • Author(s): Nomura R, Matayoshi S, Otsugu M, Kitamura T, Teramoto N, Nakano K.
  • Journal Title: Infection and Immunity Volume: - Issue: 7
  • DOI: 10.1128/iai.00897-19
  • Peer Reviewed / Open Access
• [Presentation] Evaluation of collagen-binding properties of sterilized Streptococcus mutans (2020)
  • Author(s): Suehiro Y, Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 68th Conference of Japanese Association of Dental Research
  • Int'l Joint Research
• [Presentation] 死菌処理したStreptococcus mutansのコラーゲン結合能の評価 (2020)
  • Author(s): 末廣雄登、又吉紗綾、大継將寿、野村良太、仲野和彦
  • Organizer: 第58回日本小児歯科学会大会
• [Presentation] Streptococcus mutans associated with severe dental caries induces infective endocarditis (2019)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第97回国際歯科学会
  • Int'l Joint Research
• [Presentation] Systemic evaluation of rat model of simultaneous dental caries and infective endocarditis (2019)
  • Author(s): Nomura R, Matayoshi S, Otsugu M, Kitamura T, Ooshima T, Nakano K.
  • Organizer: 第66回ヨーロッパう蝕学会
  • Int'l Joint Research
• [Presentation] Evaluation of heart conditions in rat model with severe dental caries and heart valve injury (2019)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第9回日タイ韓6大学シンポジウム
  • Int'l Joint Research
• [Presentation] 重度齲蝕によって誘発されるラット感染性心内膜炎新規モデルの構築 (2018)
  • Author(s): 又吉紗綾、大継將寿、野村良太、仲野和彦
  • Organizer: 第56回日本小児歯科学会大会
• [Presentation] Evaluation of severe dental caries induced by Streptococcus mutans during development of infective endocarditis in rats (2018)
  • Author(s): Nomura R, Otsugu M, Matayoshi S, Nakano K.
  • Organizer: 第65回ヨーロッパう蝕学会
  • Int'l Joint Research
• [Presentation] Streptococcus mutans-induced infective endocarditis in severe dental caries model rats (2018)
  • Author(s): Matayoshi S, Otsugu M, Nomura R, Nakano K.
  • Organizer: 第66回国際歯科研究学会日本部会総会・学術大会
  • Int'l Joint Research
• [Book] 生産と技術 (2020)
  • Author(s): 野村良太、仲野和彦（分担執筆）
  • Total Pages: 4
  • Publisher: 一般社団法人生産技術振興協会