• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Periodontopathic bacterial outer membrane vesicles: Biogenesis and relation to development of chronic inflammation and carcinogenesis

Research Project

Project/Area Number 20H03861
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Nakao Ryoma  国立感染症研究所, 細菌第一部, 主任研究官 (10370959)

Co-Investigator(Kenkyū-buntansha) 尾花 望  筑波大学, 医学医療系, 助教 (00722688)
川崎 忠寛  一般財団法人ファインセラミックスセンター, その他部局等, 主任研究員 (10372533)
泉福 英信  日本大学, 松戸歯学部, 教授 (20250186)
平山 悟  新潟大学, 医歯学系, 助教 (70778555)
佐々木 祐生  一般財団法人ファインセラミックスセンター, その他部局等, 上級研究員 (80808668)
上野 尚雄  国立研究開発法人国立がん研究センター, 中央病院, 医長 (90450832)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsOuter membrane vesicles / Porphyromonas gingivalis / 膜小胞 / 細菌膜小胞 / 外膜小胞 / 歯周病原細菌 / 細菌由来膜小胞 / 細菌由来外膜小胞 / 膵臓がん / 慢性炎症
Outline of Research at the Start

歯周病原細菌 Porphyromonas gingivalis (Pg)が産生する膜小胞 (BMVs) は様々な病原因子の運び屋として機能するが、Pg-BMVsの産生機構や遠隔臓器における病態形成への関与は明らかでない。歯周病と全身疾患との関連性において、Pg-BMVsが関与する可能性が考えられる。本研究では、革新的ナノイメージング技術を基軸としたアプローチにより、複雑な BMVs産生機構の全容解明を目指す。また、Pg-BMVsの生体内での運命を細胞と動物モデルを用い検討する。さらに、膵がん患者の 臨床検体からPg、およびPg-BMVsの同定を試み、Pgが関与するとされる"Dysbiosis- がん"の連関についても調査する。

Outline of Final Research Achievements

To observe the detailed structures of inside cells of Porphyromonas gingivalis (Pg), we established a combinational method of freeze fracture (FF) and scanning electron microscopy (SEM). Similar approach using the combination of FF and SEM for Pg outer membrane vesicles (OMVs) is on-going. OMV-like structures were formed on the surface of Pg when matcha green tea was added to Pg cells. In a mouse model study Pg cannot cross the blood-brain barrier (BBB), whereas OMVs likely cross the BBB and induce neurodegenerative diseases. Comparison of the total number of Pg bacteria in saliva and the ratio of Pg to total bacteria by the organ in which the patient's cancer occurred showed a trend toward higher number/rate in breast cancer patients, although no statistically significant difference was observed.

Academic Significance and Societal Importance of the Research Achievements

PgおよびPg由来OMVsは、口腔のみならず全身の健康に影響を与える可能性がある。本研究では、OMVsの産生機構、構造生物学に関する知見が蓄積された。また動物や人を対象としたPg OMVsに関する研究が推進された。PgのOMVsに関する包括的な研究によって、OMVsと慢性疾患・がんの連関解明の糸口となるような複数の成果が得られた。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (37 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (20 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Umea University(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Multimodal Inhibitory Effect of Matcha on Porphyromonas gingivalis2024

    • Author(s)
      Ryoma Nakao, Ayami Takatsuka, Kengo Mandokoro, Naoki Narisawa, Tsuyoshi Ikeda, Hideki Takai, Yorimasa Ogata
    • Journal Title

      Microbiology Spectrum

      Volume: 未定

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic <i>Escherichia coli</i> membrane vesicles2024

    • Author(s)
      Uchiyama Hiroki、Kudo Toshifumi、Yamaguchi Takehiro、Obana Nozomu、Watanabe Kenji、Abe Kimihiro、Miyazaki Hidetaka、Toyofuku Masanori、Nomura Nobuhiko、Akeda Yukihiro、Nakao Ryoma
    • Journal Title

      Human Vaccines &amp; Immunotherapeutics

      Volume: 20 Issue: 1 Pages: 2337987-2337987

    • DOI

      10.1080/21645515.2024.2337987

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of selective isolation media for detecting Actinomyces and Schaalia genera from oral specimens containing indigenous bacteria2024

    • Author(s)
      Sadao Aoki, Hiroko Yahara, Ryoma Nakao, Osamu Tsuzukibashi, Koji Yahara
    • Journal Title

      Access Microbiology

      Volume: 未定

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biofilm-derived membrane vesicles exhibit potent immunomodulatory activity in Pseudomonas aeruginosa PAO12024

    • Author(s)
      Minato Takahara, Satoru Hirayama, Hiroyuki Futamata,Ryoma Nakao, Yosuke Tashiro
    • Journal Title

      Microbiology and Immunology

      Volume: 未定

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of genes involved in enhanced membrane vesicle formation in Pseudomonas aeruginosa biofilms: surface sensing facilitates vesiculation2023

    • Author(s)
      Kanno Mizuki、Shiota Takuya、Ueno So、Takahara Minato、Haneda Keisuke、Tahara Yuhei O.、Shintani Masaki、Nakao Ryoma、Miyata Makoto、Kimbara Kazuhide、Futamata Hiroyuki、Tashiro Yosuke
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 1252155-1252155

    • DOI

      10.3389/fmicb.2023.1252155

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Scanning Electron Microscopy of Escherichia coli Encapsulated in a Spacerized Graphene Sandwich2022

    • Author(s)
      Sasaki, Yuki; Hirayama, Satoru; Nakao, Ryoma
    • Journal Title

      Microscopy

      Volume: in press Issue: 3 Pages: 175-180

    • DOI

      10.1093/jmicro/dfac010

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual Inhibitory Activity of Petroselinic Acid Enriched in Fennel Against Porphyromonas gingivalis2022

    • Author(s)
      Nanami Yoshino; Tsuyoshi Ikeda; Nakao Ryoma
    • Journal Title

      Frontiers in Microbiology

      Volume: in press

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of oral moisturizing gel containing propolis following head and neck radiotherapy: randomized controlled pilot trial2021

    • Author(s)
      Ryoma Nakao, Takao Ueno
    • Journal Title

      BDJ Open

      Volume: 7 Issue: 10 Pages: 12-12

    • DOI

      10.3390/pathogens10101286

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of pH on the properties of membrane vesicles including glucosyltransferase in Streptococcus mutans2021

    • Author(s)
      Yusuke Iwabuchi, Tomoyo Nakamura, Yasuka Kusumoto, Ryoma Nakao, Tsutomu Iwamoto, Osamu Shinozuka, Hidenobu Senpuku
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 11 Pages: 2308-2308

    • DOI

      10.3390/microorganisms9112308

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 細菌が創る膜小胞ワクチン:歯周病や感染症の制御に向けた取り組み2024

    • Author(s)
      中尾龍馬
    • Organizer
      日本小動物歯科研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] A Novel Vaccine Platform against Pneumococcal Infection Using Glycoengineered Membrane Vesicles of Probiotic Escherichia coli2024

    • Author(s)
      Ryoma Nakao
    • Organizer
      The 4th Asian Pneumococcal Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生物発光共鳴エネルギー移動を用いた細菌膜小胞の生体内観察最適化2023

    • Author(s)
      木本万結、小根山千歳、二又裕之、中尾龍馬、田代陽介
    • Organizer
      第36回日本微生物生態学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 大腸菌膜小胞のワクチン利用に向けた異種多糖抗原輸送効率の向上2023

    • Author(s)
      竹井奎多、今泉昌慶、二又裕之、中尾龍馬、田代陽介
    • Organizer
      日本膜学会 第45年会,膜シンポジウム2023の合同大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Mahanimbineは歯周病原細菌の表面にクレーター状の穴を開ける2023

    • Author(s)
      中尾龍馬、池田剛、明田幸宏
    • Organizer
      第96回日本生化学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 歯周病原細菌とその外膜小胞の構成・構造の解析2023

    • Author(s)
      高橋葵、長田勝英、中村知世、西野智彦、小林宏尚、中尾龍馬
    • Organizer
      第96回日本生化学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 膜小胞ワクチン:歯周病や感染症の制御に向けた取組み2023

    • Author(s)
      中尾龍馬
    • Organizer
      第106回日本細菌学会関東支部会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] プロバイオティクス大腸菌由来外膜小胞を使った肺炎球菌ワクチンの投与ルートの検討2023

    • Author(s)
      中尾龍馬、安部公博、山口雄大、木村聡一郎、明田幸宏
    • Organizer
      第 53 回レンサ球菌研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] フェンネルシード由来ペトロセリン酸による口腔環境改善の可能性2023

    • Author(s)
      吉野七海、小池麻里子、伊藤健吾、恩田浩之、池田剛、中尾龍馬
    • Organizer
      第77回日本栄養・食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Intranasal vaccine development using probiotic E. coli-derived membrane vesicles carrying pneumococcal capsular polysaccharides2021

    • Author(s)
      Nakao R, Iwabuchi Y, Kimura S, Hirayama S, Morino S, Suzuki M, Ohnishi M.
    • Organizer
      15th Vaccine Congress
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グリシンにより誘導された細菌メンブレンベシクルの性質とアジュバント活性の解析2021

    • Author(s)
      平山悟、中尾龍馬
    • Organizer
      第63回歯科基礎医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌由来メンブレンベシクルによる宿主免疫を介した宿主微生物叢制御2021

    • Author(s)
      奥田真由、尾花 望、奥脇響、中尾 龍馬、泉福 英信、野村 暢彦
    • Organizer
      第34回微生物生態学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Prospective vaccine strategy using bacterial membrane vesicles delivered into nasal cavity2021

    • Author(s)
      Ryoma Nakao
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of anti-TB vaccine using mycobacterial membrane vesicles2021

    • Author(s)
      Takehiro Yamaguchi, Noriaki Samukawa, Ryoma Nakao and Shuhei Tomita
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of initial pH conditions on the membrane vesicles produced by Streptococcus mutans2021

    • Author(s)
      Yusuke Iwabuchi, Tomoyo Nakamura, Yasuka Kusumoto, Ryoma Nakao, Tsutomu Iwamoto, Osamu Shinozuka, Hidenobu Senpuku
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on glucosyltransferase of Streptococcus mutans2021

    • Author(s)
      Tomoyo Nakamura, Naoki Narisawa, Fumio Takenaga, Ryoma Nakao, and Hidenobu Senpuku
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of mucosal immunization of Clostridium perfringens membrane vesicles on humoral immunity and gut microbiota2021

    • Author(s)
      Okuda Mayu, Obana Nozomu, Okuwaki Hibiki, Nakao Ryoma, Senpuku Hidenobu, Nomura Nobuhiko
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of immunomodulatory membrane vesicles derived from Pseudomonas aeruginosa biofilm2021

    • Author(s)
      Minato Takahara, Satoru Hirayama, Ryoma Nakao, Hiroyuki Futamata, Yosuke Tashiro
    • Organizer
      EMBO Workshop: Bacterial Membrane Vesicles: Biogenesis, functions, and medical applications
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory activity of mahanimbine against Porphyromonas gingivalis2021

    • Author(s)
      Ryoma Nakao, Tsuyoshi Ikeda
    • Organizer
      日本分子生物学会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 外来性莢膜多糖を発現するプロバイオティクス大腸菌が作る膜小胞ワクチンの特性評価2021

    • Author(s)
      Ryoma Nakao, Hiroaki Kobayashi, Yusuke Iwabuchi, Yusuke Sasaki, Madeleine Ramstedt, Satoru Hirayama, Makoto Ohnishi
    • Organizer
      第15回 日本ワクチン学会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Book] Methods in Molecular Biology: Glycine Induction Method: Effective Production of Immunoactive Bacterial Membrane Vesicles with Low Endotoxin Content2022

    • Author(s)
      Hirayama S, Nakao R.
    • Publisher
      Springer Nature
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Book] Methods in Molecular Biology: Intranasal vaccine study using Porphyromonas gingivalis membrane vesicles: isolation method and application to a mouse model2021

    • Author(s)
      Hirayama S, Nakao R.
    • Publisher
      Springer Nature
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] EMBO Workshop on Bacterial Membrane Vesicles

    • URL

      https://meetings.embo.org/event/20-membrane-vesicles

    • Related Report
      2021 Annual Research Report
  • [Remarks] EMBO Workshop on MVs 2021 Poster

    • URL

      https://meetings.embo.org/files/posters/20-membrane-vesicles.pdf

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] プロバイオティクス大腸菌の二重変異株、該二重変異株から産生される膜小胞、及びそれを用いた製品2024

    • Inventor(s)
      中尾 龍馬、安部 公博、尾花 望、渡辺 賢二
    • Industrial Property Rights Holder
      国立感染症研究所長
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2024-033964
    • Filing Date
      2024
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] バチルス属細菌の膜小胞を基盤とする担体及びそれを用いた製品2024

    • Inventor(s)
      安部 公博、中尾龍馬
    • Industrial Property Rights Holder
      国立感染症研究所長
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2024-037222
    • Filing Date
      2024
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi