The discovery of molecules that inhibit oral biofilm formation by inhibiting cell-to-cell communication

• Project/Area Number: 20390537
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: TAKEHARA Tadamichi Kyushu Dental College, 歯学部, 名誉教授 (00038879)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Akihiro 九州歯科大学, 歯学部, 助教 (20364151) ; ANSAI Toshihiro 九州歯科大学, 歯学部, 准教授 (80244789) ; AWANO Shuji 九州歯科大学, 歯学部, 講師 (20301442) ; SOH Inho 九州歯科大学, 歯学部, 助教 (10285463) ; 濱嵜 朋子 九州歯科大学, 歯学部, 助教 (60316156)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2008: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 細菌間シグナル / クオラムセンシング / バイオフィルム / 口腔細菌 / 阻害剤

Research Abstract

We initially produced several analogues by modifying the chemical structures of autoinducer-2 (AI-2). We examined the inhibitory activities of these analogues by examining the luminescence activities of Vibrio harveyi, a luminescent marine bacterium species. Of the analogues synthesized, we chose those that inhibited the luminescence activities of V.harveyi. Using the selected analogues, we analyzed the inhibitory effects of these analogues on biofilm formation by oral streptococci, including Streptococcus mutans, a human cariogenic species. Some of the analogues inhibited biofilm formation by these bacteria, although some of the analogues that inhibited biofilm formation by S. mutans did not inhibit biofilm formation by other streptococci. We could not find a common inhibitor for all oral streptococci. Now we are analyzing the role of these analogues in the expression of S.mutans glucosyltransferase (GTF) genes and their function in biofilm formation by S.mutans.

Research Products

• [Journal Article] Streptococcus anginosus L-cysteine desulfhydrase gene expression is associated with abscess formation in BALB/c mice. (2011)
  • Author(s): Takahashi, Y., Yoshida, A., Nagata, E., Hoshino, T., Oho, T., Awano, S., Takehara, T., Ansai, T.
  • Journal Title: Molecular Oral Microbiol. 26 Pages: 221-227
• [Journal Article] Rapid LED-based fluorescence microscopy distinguishes between live and dead bacteria in oral clinical samples. (2010)
  • Author(s): Masakiyo, Y., Yoshida, A., Takahashi, Y., Shintani, Y., Awano, S., Ansai, T., Sawayama, S., Shimakita, T., Takehara, T.
  • Journal Title: Biomed Res. 31 Pages: 21-26
  • NAID: 130004903779
• [Journal Article] The identification of genes specific to Prevotella intermedia and Prevotella nigrescens using genomic subtractive hybridization. (2010)
  • Author(s): Masakiyo, Y., Yoshida, A., Shintani, Y., Takahashi, Y., Ansai, T., Takehara, T.
  • Journal Title: Anaerobe 16 Pages: 265-269
• [Journal Article] The identification of genes specific to Prevotella intermedia and Prevotella nigrescens using genomic subtractive hybridization (2010)
  • Author(s): Masakiyo, Y., Yoshida.A., Shintani, Y., Takahashi, Y., Ansai, t., Takehara, T
  • Journal Title: Anaerobe Volume: 16 Pages: 265-269
  • Peer Reviewed
• [Journal Article] Rapid LED-based fluorescence microscopy distinguishes between live and dead bacteria in oral clinical samples. (2010)
  • Author(s): Masakiyo, Y., Yoshida.A., Takahashi, Y., Shintani, Y., Awano, S., Ansai, T., Sawayama, S., Shimakita, T., Takehara, T
  • Journal Title: Biomed Res. Volume: 31 Pages: 21-26
  • NAID: 130004903779
  • Peer Reviewed
• [Journal Article] Rapid LED-based fluorescence microscopy distinguishes between live and dead bacteria in oral clinical samples (2010)
  • Author(s): Masakiyo, Y., Yoshida, A., Takahashi, Y., Shintani, Y., Awano, S., Ansai, T., Sawayama, S., Shimakita, T., Takehara, T.
  • Journal Title: Biomed Res. 31 Pages: 21-26
  • NAID: 130004903779
  • Peer Reviewed
• [Journal Article] Hydrogen sulfide production from cysteine and homocysteine by periodontal and oral bacteria. (2009)
  • Author(s): Yoshida, A., Yoshimura, M., Ohara, N., Yoshimura, S., Nagashima, S., Takehara, T., Nakayama, K.
  • Journal Title: J Periodontol. 80 Pages: 1845-1851
• [Journal Article] Hydrogen sulfide production from cysteine and homocysteine by periodontal and oral bacteria. (2009)
  • Author(s): Yoshida, A., Yoshimura, M., Ohara, N., Yoshimura, S., Nagashima, S., Takehara, T.
  • Journal Title: J.Periodontology 80 Pages: 1845-1851
  • Peer Reviewed
• [Journal Article] Identification of the genes associated with a virulent strain of Porphyromonas gingivalis using the subtractive hybridization technique. (2008)
  • Author(s): Tachibana-Ono, M., Yoshida, A., Kataoka, S., Ansai, T., Shintani, Y., Takahashi, Y., Toyoshima, K., Takehara, T.
  • Journal Title: Oral Microbiol. Immunol. 23 Pages: 84-87
• [Journal Article] Identification of the genes associated with a virulent strain of Porphyromonas gineivalis usine the subtractive hybridization techniaue (2008)
  • Author(s): Tachibana-Ono, M., Yoshida, A., Takehara T., et al
  • Journal Title: Oral Microbiol. Immunol. 23 Pages: 84-87
  • Peer Reviewed
• [Journal Article] The prevalence of periodontopathogenic bacteria in saliva is linked to periodontal health status and oral malodour (2008)
  • Author(s): Kurata, H., Awano, S., Yoshida A., Takehara. T., et al
  • Journal Title: J. Med. Microbiology 57 Pages: 636-642
  • Peer Reviewed
• [Journal Article] The identification of genes specific to Prevotella intermedia and Prevotella nigrescens using genomic subtractive hybridization
  • Author(s): Masakiyo, Y., Yoshida, A., Shintani, Y., Takahashi, Y., Ansai, t., Takehara, T
  • Journal Title: Anaerobe (印刷中)
  • Peer Reviewed
• [Presentation] マウス膿瘍形成におけるStreptococcus anginosus ss C-S liase 遺伝子の発現解析 (2010)
  • Author(s): 高橋優介、吉田明弘、新谷泰之、粟野秀慈、安細敏弘
  • Organizer: 第70回九州歯科学会総会(2010)(九州歯会誌64:139
  • Place of Presentation: 北九州
• [Presentation] Streptococcus mutansの生菌と死菌/損傷菌を区別した定量検出法の開発 (2010)
  • Author(s): 正清義朗、吉田明弘、高橋優介、安細敏弘
  • Organizer: 第59回日本口腔衛生学会・総会
  • Place of Presentation: 新潟
• [Presentation] 生菌・死菌を区別した根管内細菌の定量検出法の開発 (2010)
  • Author(s): 高橋優介、吉田明弘、粟野秀慈、安細敏弘
  • Organizer: 第59回日本口腔衛生学会・総会
  • Place of Presentation: 新潟
• [Presentation] Streptococcus anginosus bC-S lyase gene expression and experimental abscess formation. (2010)
  • Author(s): Yoshida A., Takahashi Y., Nagata, E., Hoshino, T., Oho, T., Awano S., Ansai T.
  • Organizer: 第88回IADR
  • Place of Presentation: Centre Convencions Internacional Barcelona
• [Presentation] Streptococcus anginosus βC-S lyase gene expression and experimental abscess formation (2010)
  • Author(s): Yoshida.A., Takahashi, Y., Nagata, E., Hoshino, T., Oho, T., Awano, S., Ansai, T.
  • Organizer: 第88回International Association for Dental Research
  • Place of Presentation: Centre Convencions Internacional Barcelona
• [Presentation] マウス実験膿瘍におけるStreptococcus anginos us lcd遺伝子の発現解析 (2010)
  • Author(s): 吉田明弘、高橋優介、長田恵美、於保孝彦、粟野秀慈、安細敏弘
  • Organizer: 第59回日本口腔衛生学会・総会
  • Place of Presentation: 新潟
• [Presentation] 生菌と死菌/損傷菌を区別した定量的口腔細菌検出法の開発 (2009)
  • Author(s): 吉田明弘
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Quantitative analysis of Streptococcus anginosus lcd gene expression in the tongue coat. (2009)
  • Author(s): 高橋優介, 吉田明弘, 新谷泰之, 正清義明, 粟野秀慈, 安細敏弘, 竹原直道
  • Organizer: ISBOR
  • Place of Presentation: Germany
• [Presentation] Porphyromonas gingivalis mgl gene expression in the tongue coat. (2009)
  • Author(s): 新谷泰之, 吉田明弘, 高橋優介, 正清義明, 粟野秀慈, 安細敏弘, 竹原直道
  • Organizer: ISBOR
  • Place of Presentation: Germany
• [Presentation] 蛍光染色フィルタ法を用いた根管内細菌の迅速定量 (2009)
  • Author(s): 高橋優介、吉田明弘、正清義明、安細敏弘、粟野秀慈、新谷泰之、竹原直道
  • Organizer: 第31回日本口腔衛生学会九州地方会総会
  • Place of Presentation: 九州歯科大学講堂
• [Presentation] The prevalence ofperiodontopathic bacteriain patients withchronic kidney disease. (2009)
  • Author(s): Yoshida A., Awano S., Ansai T., Masakiyo, Teratani, G., Soh, I., Hamasaki, T., Takehara T.
  • Organizer: The 9th WorldCongress on Preventive Dentistry
  • Place of Presentation: Phuket, Thailand
• [Presentation] 口腔細菌のクオラムセンシングとバイオフィルム形成.シンポジウム「バイオフィルム研究の最前線:制御を目指して」 (2009)
  • Author(s): 吉田明弘
  • Organizer: 第61回日本生物工学会大会
  • Place of Presentation: (名古屋大学)名古屋
• [Presentation] う蝕細菌のクオラムセンシング.シンポジウム「細菌の生存戦略をめぐるあらたな展開」 (2009)
  • Author(s): 吉田明弘
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド・神戸
• [Presentation] 口腔細菌のクオラムセンシングとバイオフィルム形成シンポジウム「バイオフィルム研究の最前線:制御を目指して」 (2009)
  • Author(s): 吉田明弘
  • Organizer: 第61回日本生物工学会大会
  • Place of Presentation: 名古屋大学
• [Presentation] う蝕細菌のクオラムセンシング.シンポジウム「細菌の生存戦略をめぐるあらたな展開」 (2009)
  • Author(s): 吉田明弘
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] Streptococcus gordoniiと共培養時におけるStreptococcus mutansバイオフィルムでの遺伝子発現 (2008)
  • Author(s): 吉田明弘、安細敏弘
  • Organizer: 第81回日本細菌学会総会
  • Place of Presentation: (国立京都国際会館)京都
• [Presentation] Transcriptional Profiling of Streptococcus mutans Biofilms Co-cultured with Streptococcus gordonii. (2008)
  • Author(s): Yoshida A.,, Kuramitsu, H.K., Takehara T.
  • Organizer: 86th General Session & Exhibition of the IADR
  • Place of Presentation: Metro Toronto Convention Centre, ON, Canada
• [Presentation] Streptococcus gordonii存在下におけるStreptococcus mutansバイオフィルムでの遺伝子発現 (2008)
  • Author(s): 吉田明弘、安細敏弘
  • Organizer: 第50回歯科基礎医学会学術大会・総会
  • Place of Presentation: (TOC有明コンベンションホール)東京
• [Presentation] 舌苔における口臭関連遺伝子の発現解析 (2008)
  • Author(s): 新谷泰之、吉田明弘、高橋優介、正清義朗、粟野秀慈、安細敏弘、竹原直道
  • Organizer: 第57回日本口腔衛生学会総会
  • Place of Presentation: (大宮ソニックシティ)埼玉
• [Presentation] 蛍光染色フィルタ法を用いた口腔細菌の迅速定量 (2008)
  • Author(s): 正清義朗、吉田明弘、安細敏弘、新谷泰之、高橋優介、竹原直道
  • Organizer: 第57回日本口腔衛生学会総会
  • Place of Presentation: (大宮ソニックシティ)埼玉
• [Presentation] Transcriptional Profiling of Streptococcus mutans Biofilms Co-cultured with Streptococcus gordonii (2008)
  • Author(s): Yoshida, A. Takehara, T., et al
  • Organizer: 86th General Session & Exhibition of the IADR
  • Place of Presentation: Metro Toronto Convention Centre, on, Canada
• [Book] 必修臨床研修歯科医ハンドブック(平成22年度版) (2010)
  • Author(s): 粟野秀慈、吉田明弘、邵仁浩、安細敏弘
  • Publisher: 医歯薬出版
• [Book] 衛生学・公衆衛生学.宮武光吉,渡邊達夫ほか編,第17章高齢者保健(p.211-p.216) (2008)
  • Author(s): 竹原直道
  • Publisher: 医歯薬出版
• [Book] 2.グラム陰性細菌のクオラムセンシングとバイオフィルムの関係を利用した抗菌剤の可能性(p.264-p.277).『バイオフィルムの基礎と制御』第2編応用編1形成防止、除去技術、第2章バイオフィルム形成防止具体事例、第4節バイオフィルム形成阻害剤 (2008)
  • Author(s): 中山二郎、吉田明弘
  • Publisher: 株式会社エヌ・ティー・エス
• [Book] 第IV部基礎編,第9章う蝕の歴史.(231p-236p)田上順次ら編:う蝕学ーチェアサイドの予防と回復のプログラムー (2008)
  • Author(s): 竹原直道
  • Publisher: 永末書店
• [Book] 今日からはじめる!口腔乾燥症の臨床-この主訴にこのアプローチー安細敏弘、柿木保明編集 (2008)
  • Author(s): 粟野秀慈、吉田明弘
  • Publisher: 医歯薬出版
• [Remarks] ホームページ等
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