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Novel pathogenic mechanisms for the control of systemic diseases induced by cariogenic bacteria

Research Project

Project/Area Number 21H03149
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionOsaka University

Principal Investigator

Nakano Kazuhiko  大阪大学, 大学院歯学研究科, 教授 (00379083)

Co-Investigator(Kenkyū-buntansha) 大継 將寿  大阪大学, 大学院歯学研究科, 助教 (40803086)
野村 良太  広島大学, 医系科学研究科(歯), 教授 (90437385)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2021: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
KeywordsStreptococcus mutans / コラーゲン結合タンパク / 感染性心内膜炎 / 急性脳出血 / 脳動脈瘤 / IgA腎症 / カイコモデル / 菌体表層構造 / 唾液検体 / PCR法 / エックス線結晶構造解析 / コラーゲン結合ドメイン / ミュータンスレンサ球菌 / 口腔サンプル / 抗菌薬 / 脳血管疾患 / 微小出血 / Gd-IgA1 / 循環器疾患 / 微小脳出血 / 死菌 / ミュータンスレンサ細菌 / デンタルプラーク
Outline of Research at the Start

本研究では、10施設の歯学部附属病院にご協力いただき、健常者および全身疾患に罹患した患者の口腔内におけるコラーゲン結合タンパク(Collagen-binding protein; CBP)の分布に関する全国調査を行う。調査により得られた菌株を死菌処理して、in-vitro系、ex-vivo系を用いた各種全身疾患における病原メカニズムの解明を行う。さらに、in-vivo系の各実験系を応用してCBP陽性菌株の病原性の評価を行うとともに、CBP陽性菌の病原性を不活化する方法の検討を行い、CBP陽性菌による感染症の新たな治療法開発へとつながる基盤を創出する。

Outline of Final Research Achievements

Streptococcus mutans expressing a 120 kDa collagen-binding protein (CBP) is associated with the pathology of cerebrovascular diseases such as acute cerebral hemorrhage and cerebral aneurysm, and kidney diseases such as IgA nephropathy and IgA vasculitis. When evaluating the systemic pathogenicity of CBP-positive S. mutans using silkworm larvae, not only live bacteria but also killed bacteria treated with antibiotics reduced the survival rate of silkworms. From the detailed analysis of the cell surface structure of CBP-positive S. mutans, CBP may be involved in changes in the cell surface properties of the bacteria.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、口腔内に存在するCBP 陽性S. mutansがある種の脳血管疾患や腎疾患の増悪化に関わることが明らかとなった。このことから、口腔衛生状態を良好に保ちCBP 陽性のS. mutansの減少に努めることが、全身疾患の予防において重要であることを示すことができた。また、本研究で示したCBP 陽性S. mutansに特異的な菌体表層構造は、今後の病原メカニズムの解明や治療法の開発において活用できるものと考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (42 results)

All 2024 2023 2022 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (28 results) (of which Int'l Joint Research: 12 results)

  • [Journal Article] Inhibitory Effects of Shikonin Dispersion, an Extract of Lithospermum erythrorhizon Encapsulated in β-1,3-1,6 Glucan, on Streptococcus mutans and Non-Mutans Streptococci2024

    • Author(s)
      Nomura Ryota、Suehiro Yuto、Tojo Fumikazu、Matayoshi Saaya、Okawa Rena、Hamada Masakazu、Naka Shuhei、Matsumoto-Nakano Michiyo、Unesaki Rika、Koumoto Kazuya、Kawauchi Keiko、Nishikata Takahito、Akitomo Tatsuya、Mitsuhata Chieko、Yagi Masatoshi、Mizoguchi Toshiro、Fujikawa Koki、Taniguchi Taizo、Nakano Kazuhiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 25 Issue: 2 Pages: 1075-1075

    • DOI

      10.3390/ijms25021075

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?2024

    • Author(s)
      Nakatogawa H., Hokamura K., Nomura R., Nakano K., Umemura K., Morita A., Homma Y., Tanaka T.
    • Journal Title

      Cerebrovascular Diseases

      Volume: - Pages: 1-7

    • DOI

      10.1159/000536203

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Rat Caries-Induced Pulpitis Model for Vital Pulp Therapy2023

    • Author(s)
      Huang H.、Okamoto M.、Watanabe M.、Matsumoto S.、Moriyama K.、Komichi S.、Ali M.、Matayoshi S.、Nomura R.、Nakano K.、Takahashi Y.、Hayashi M.
    • Journal Title

      Journal of Dental Research

      Volume: ‐ Issue: 5 Pages: 574-582

    • DOI

      10.1177/00220345221150383

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibitory Effect of Adsorption of Streptococcus mutans onto Scallop-Derived Hydroxyapatite2023

    • Author(s)
      Usuda Momoko、Kametani Mariko、Hamada Masakazu、Suehiro Yuto、Matayoshi Saaya、Okawa Rena、Naka Shuhei、Matsumoto-Nakano Michiyo、Akitomo Tatsuya、Mitsuhata Chieko、Koumoto Kazuya、Kawauchi Keiko、Nishikata Takahito、Yagi Masatoshi、Mizoguchi Toshiro、Fujikawa Koki、Taniguchi Taizo、Nakano Kazuhiko、Nomura Ryota
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 14 Pages: 11371-11371

    • DOI

      10.3390/ijms241411371

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structure, Stability and Binding Properties of Collagen-Binding Domains from Streptococcus mutans2023

    • Author(s)
      Nishi Akari、Matsui Hikaru、Hirata Azumi、Mukaiyama Atsushi、Tanaka Shun-ichi、Yoshizawa Takuya、Matsumura Hiroyoshi、Nomura Ryota、Nakano Kazuhiko、Takano Kazufumi
    • Journal Title

      Chemistry

      Volume: 5 Issue: 3 Pages: 1911-1920

    • DOI

      10.3390/chemistry5030130

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous Presence of Campylobacter rectus and Cnm-Positive Streptococcus mutans in the Oral Cavity Is Associated with Renal Dysfunction in IgA Nephropathy Patients: 5-Year Follow-Up Analysis.2023

    • Author(s)
      Misaki T, Naka S, Nagasawa Y, Matsuoka D, Ito S, Nomura R, Matsumoto-Nakano M, Nakano K
    • Journal Title

      Nephron

      Volume: 13 Issue: 3-4 Pages: 134-143

    • DOI

      10.1159/000525511

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] cnm-positive Streptococcus mutans is associated with galactose-deficient IgA in patients with IgA nephropathy2023

    • Author(s)
      Misaki T, Naka S, Suzuki H, Lee M, Aoki R, Nagasawa Y, Matsuoka D, Ito S, Nomura R, Matsumoto-Nakano M, Suzuki Y, Nakano K.
    • Journal Title

      Plos One

      Volume: - Issue: 3 Pages: 0-0

    • DOI

      10.1371/journal.pone.0282367

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple-ion releasing bioactive surface pre-reacted glass-ionomer (S-PRG) filler: Innovative technology for dental treatment and care2023

    • Author(s)
      Imazato S, Nakatsuka T, Kitagawa H, Sasaki J, Yamaguchi S, Ito S, Takeuchi H, Nomura R, Nakano K.
    • Journal Title

      Journal of Functional Biomaterials

      Volume: 14(4) Issue: 4 Pages: 236-236

    • DOI

      10.3390/jfb14040236

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Harboring Cnm‐expressing <i>Streptococcus mutans</i> in the oral cavity relates to both deep and lobar cerebral microbleeds2023

    • Author(s)
      Ikeda Shuhei、Saito Satoshi...
    • Journal Title

      European Journal of Neurology

      Volume: - Issue: 11 Pages: 3487-3496

    • DOI

      10.1111/ene.15720

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cnm of Streptococcus mutans is important for cell surface structure and membrane permeability2022

    • Author(s)
      Naka S, Matsuoka D, Goto K, Misaki T, Nagasawa Y, Ito S, Nomura R, Nakano K, Matsumoto-Nakano M
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: - Pages: 994014-994014

    • DOI

      10.3389/fcimb.2022.994014

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics of children and guardians possessing CBP-positive Streptococcus mutans strains: a cross-sectional study2022

    • Author(s)
      Otsugu Masatoshi、Mikasa Yusuke、Kitamura Takahiro、Suehiro Yuto、Matayoshi Saaya、Nomura Ryota、Nakano Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17510-17510

    • DOI

      10.1038/s41598-022-22378-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the collagen-binding properties and virulence of killed Streptococcus mutans in a silkworm model2022

    • Author(s)
      Suehiro Y, Nomura R, Matayoshi S, Otsugu M, Iwashita N,Nakano K.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 2800-2800

    • DOI

      10.1038/s41598-022-06345-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections2021

    • Author(s)
      Oliveira LT, Alves LA, Harth-Chu EN, Nomura R, Nakano K, Mattos-Graner RO.
    • Journal Title

      Journal of Medical Microbiology

      Volume: 70 Issue: 12 Pages: 12-12

    • DOI

      10.1099/jmm.0.001457

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] cnm-Positive Streptococcus mutans and diffusion-weighted imaging hyperintensities in acute intracerebral hemorrhage2020

    • Author(s)
      Yuji Shiga, Shiro Aoki, Naohisa Hosomi, Ryota Nomura, Masahiro Nakamori, Tomohisa Nezu, Keisuke Tachiyama, Teppei Kamimura, Naoto Kinoshita, Ryo Shimomura, Yuki Hayashi, Hayato Matsushima, Eiji Imamura, Hiroki Ueno, Shinichi Wakabayashi, Kazuhiko Nakano, Tatsuo Kohriyama, Hirofumi Maruyama
    • Journal Title

      Eur J Neurol .

      Volume: - Issue: 5 Pages: 1581-1589

    • DOI

      10.1111/ene.14725

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Interaction of essential oils in Citrus unshiu to cause inhibition of Streptococcus mutans bacterial growth2023

    • Author(s)
      Okuda M., Ohata J., Matayoshi S., Nomura R., Nakano K.
    • Organizer
      Korean Academy of Pediatric Dentistry 2023 Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Contributions of Streptococcus mutans to dental caries and infective endocarditis2023

    • Author(s)
      Suehiro Y., Matayoshi S., Otsugu M., Nomura R., Nakano K.
    • Organizer
      Korean Academy of Pediatric Dentistry 2023 Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IgA adherence to Streptococcus mutans Cnm for IgA nephropathy onset2023

    • Author(s)
      Matsuoka D., Suehara K., Naka S., Misaki T., Nagasawa Y., Ito S., Nomura R., Nakano K.
    • Organizer
      101st General Session & Exhibition of the IADR
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum agglutinating ability of Streptococcus mutans killed by antibiotic2023

    • Author(s)
      Suehiro Y., Matayoshi S., Otsugu M., Nomura R., Nakano K.
    • Organizer
      101st General Session & Exhibition of the IADR
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory effects of S-PRG filler eluate on acid tolerance of Streptococcus mutans2023

    • Author(s)
      Usuda M., Kametani M., Akitomo T., Nakano M., Suehiro Y., Matayoshi S., Mitsuhata C., Nakano K., Nomura R.
    • Organizer
      29th IAPD Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathogenicity of collagen-binding protein in Streptococcus mutans2023

    • Author(s)
      Matsuoka D., Naka S., Goto K., Nomura R., Nakano K., Matsumoto-Nakano M.
    • Organizer
      29th IAPD Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cariology and systemic disorder collagen-binding properties of killed Streptococcus mutans strains2023

    • Author(s)
      Suehiro Y., Matayoshi S., Otsugu M., Nomura R., Nakano K.
    • Organizer
      29th IAPD Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of killed Streptococcus mutans strains by fluorescence microscopy2023

    • Author(s)
      Mikasa Y., Suehiro Y., Matayoshi S., Otsugu M., Nomura R., Nakano K.
    • Organizer
      32nd Annual Conference of the Taiwan Academy of Pediatric Dentistry
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Possible mediation of tonsils to IgA nephropathy caused by cnm-positive Streptococcus mutans, a major pathogen of dental caries2023

    • Author(s)
      Misaki T., Naka S., Nagasawa Y., Matsuoka D., Matayoshi S., Ito S., Nomura R., Matsumoto-Nakano M., Nakano K.
    • Organizer
      17th International symposium on IgA nephropathy (IIgAN)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] cnm-positive Streptococcus mutans, a major pathogen of dental caries may cause IgA nephropathy via tonsils2023

    • Author(s)
      Misaki T., Naka S., Nagasawa Y., Matsuoka D., Matayoshi S., Ito S., Nomura R., Matsumoto-Nakano M., Nakano K.
    • Organizer
      The Kidney Week 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Collagen-binding protein pathogenicity in rat model of IgA nephropathy2023

    • Author(s)
      Suehara K., Matsuoka D., Naka S., Misaki T., Nagasawa Y., Ito S., Nomura R., Nakano K., Matsumoto-Nakano M.
    • Organizer
      Japanese Association for Dental Research (JADR)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory mechanisms of S-PRG filler eluate on Streptococcus mutans in the presence of sucrose2023

    • Author(s)
      Usuda M., Kametani M., Akitomo T., Nakano M., Suehiro Y., Matayoshi S., Mitsuhata C., Nakano K., Nomura R.
    • Organizer
      第61回日本小児歯科学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 死菌処理によるStreptococcus mutansのコラーゲン結合能への影響2023

    • Author(s)
      末廣雄登,又吉紗綾,大継將寿,野村良太,仲野和彦
    • Organizer
      第61回日本小児歯科学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] コラーゲン結合タンパクCnmとヒトIgAの結合に関する分子生物学的検討2023

    • Author(s)
      松岡大貴,仲 周平,後藤花奈,野村良太,仲野和彦,仲野道代
    • Organizer
      第61回日本小児歯科学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 小児におけるコラーゲン結合タンパク陽性Streptococcus mutans株の分布と齲蝕罹患との関係2023

    • Author(s)
      奥田真琴,又吉紗綾,東條文和,仲 周平,仲野道代,野村良太,仲野和彦
    • Organizer
      第61回日本小児歯科学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔内のcnm遺伝子陽性S. mutansとIgA腎症患者の糖鎖異常IgA沈着の関連性2023

    • Author(s)
      三﨑 太郎, 仲 周平, 鈴木 仁, 李 明峰, 青木 良輔, 長澤 康行, 松岡 大貴, 伊藤 誓悟, 野村 良太, 仲野 道代, 鈴木 祐介, 仲野 和彦
    • Organizer
      第 66 回日本腎臓学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 廃棄される貝殻から生成したハイドロキシアパタイトの Streptococcus mutans に対する抑制効果メカニズムの検討2023

    • Author(s)
      金木亜美,小川将史,臼田桃子,亀谷茉莉子,秋友達哉,末廣雄登,又吉紗綾,仲 周平,大川玲奈,光畑智恵子,仲野道代,仲野和彦,野村良太
    • Organizer
      第42回日本小児歯科学会中四国地方会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 柑橘果皮エキスの Streptococcus mutans に対する抗菌効果の検討2023

    • Author(s)
      日下 知,秋友達哉,臼田桃子,亀谷茉莉子,光畑智恵子,仲野和彦,野村良太
    • Organizer
      第42回日本小児歯科学会中四国地方会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 口腔内のcnm遺伝子陽性S. mutansとC. rectusの存在はIgA腎症患者の5年後の腎機能の増悪に影響する2022

    • Author(s)
      三﨑太郎、長澤康行、仲周平、松岡大貴、和唐薫子、伊藤誓悟、野村良太、仲野道代、仲野和彦
    • Organizer
      第44回IgA腎症研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] う蝕原性細菌Streptococcus mutansの菌体表層に発現するコラーゲン結合タンパク(Cnm)がIgA腎症様腎炎発症に関連する可能性2022

    • Author(s)
      仲 周平、松岡大貴、和唐薫子、三﨑太郎、後藤花奈、長澤康行、伊藤誓悟、野村良太、仲野道代、仲野和彦
    • Organizer
      第44回IgA腎症研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗菌薬により死菌処理したStreptococcus mutansのコラーゲン結合能の分析2022

    • Author(s)
      末廣雄登、又吉紗綾、大継將寿、野村良太、仲野和彦
    • Organizer
      第60回日本小児歯科学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Streptococcus mutansコラーゲン結合タンパクCnmの病原性に関する検討2022

    • Author(s)
      松岡大貴、仲 周平、後藤花奈、野村良太、仲野和彦、仲野道代
    • Organizer
      第60回日本小児歯科学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ホタテ貝由来アパタイトのStreptococcus mutansに対する齲蝕原性抑制効果の検討2022

    • Author(s)
      臼田桃子、亀谷茉莉子、秋友達哉、末廣雄登、又吉紗綾、中野将志、光畑智恵子、仲 周平、仲野道代、仲野和彦、野村良太
    • Organizer
      第41回日本小児歯科学会近畿地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] シコニンの齲蝕原性細菌および口腔レンサ球菌に対する抗菌効果の検討2022

    • Author(s)
      末廣雄登、又吉紗綾、野村良太、仲野和彦
    • Organizer
      第41回日本小児歯科学会近畿地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] スクロース存在下におけるS-PRGフィラー溶出液のStreptococcus mutansに対する抑制効果の検討2022

    • Author(s)
      亀谷茉莉子、臼田桃子、秋友達哉、中野将志、末廣雄登、又吉紗綾、光畑智恵子、仲野和彦、野村良太
    • Organizer
      第41回日本小児歯科学会中四国地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Collagen-binding properties of Streptococcus mutans killed by amoxicillin2021

    • Author(s)
      Suehiro Y, Matayoshi S, Otsugu M, Nomura R, Nakano K.
    • Organizer
      69th Conference of Japanese Association of Dental Research
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 死菌処理したStreptococcus mutansの感染性心内膜炎に対する病原性の評価2021

    • Author(s)
      末廣雄登、又吉紗綾、大継將寿、野村良太、仲野和彦
    • Organizer
      第59回日本小児歯科学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 死菌処理したStreptococcus mutansの感染性心内膜炎に対する病原性の評価2021

    • Author(s)
      末廣雄登、又吉紗綾、大継將寿、野村良太、仲野和彦
    • Organizer
      第40回日本小児歯科学会大会近畿地方会大会
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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