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Development of antipathogenic agents targeting quorum sensing of Gram-positive bacteria

Research Project

Project/Area Number 24380050
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied microbiology
Research InstitutionKyushu University

Principal Investigator

NAKAYAMA Jiro  九州大学, (連合)農学研究科(研究院), 准教授 (40217930)

Co-Investigator(Kenkyū-buntansha) NAGATA Koji  東京大学, 大学院農学生命科学研究科, 准教授 (30280788)
IGARASHI Yasuhiro  富山県立大学, 工学部, 教授 (20285159)
SUZUKI Takashi  愛媛大学, 医学部附属病院, 講師 (70398048)
SHIMIZU Tohru  金沢大学, 医学系, 教授 (80235655)
OHTANI Kaori  金沢大学, 医学系, 講師 (30377410)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywordsクオラムセンシング / グラム陽性細菌 / 日和見感染 / 抗感染症剤 / ペプチドデザイン / 阻害剤開発 / クォルモン / アンタゴニスト / グラム陽性日和見感染菌 / 阻害剤スクリーニング / デプシペプチド / ゼラチナーゼ / 眼内炎
Outline of Final Research Achievements

Quorum sensing mediated by cyclic peptide as an autoinducer (AIP) commonly controls the expression of virulence in pathogenic Gram-positive bacteria such as staphylococci, enterococci and clostridia. In this study, we performed screening and drug design of quorum sensing inhibitors (QSI). Consequently, we found that a number of cyclic peptides of microbial secondary metabolites, e.g., WS9326A and Avellanin C, showed antagonistic activity against AIP at micromolar concentrations and attenuated virulences of Gram-positive pathogens. Further, we succeeded in designing of QSI peptides based on the structure of AIP of Clostridium perfringens, which attenuated the expression of theta toxin gene at submicromolar concentrations

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012 2011

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) Book (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Avellanin C, an inhibitor of quorum sensing signaling in Staphylococcus aureus, from Hamigera ingelheimensis2015

    • Author(s)
      Yasuhiro Igarashi, Fumiya Gohda, Taito Kadoshima, Takao Fukuda, Tomoaki Hanafusa, Akane Shojima, Jiro Nakayama, Gerald F. Bills, Steven Williams
    • Journal Title

      Journal of Antibiotics

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of a peptide antagonist against fsr quorum sensing of Enterococcus faecalis.2013

    • Author(s)
      Jiro Nakayama, Ryoji Yokohata, Mami Sato, Takashi Suzuki, Takahisa Matsufuji, Kenzo Nishiguchi, Takeshi Kawai, Yosuke Yamanaka, Koji Nagata, Masaru Tanokura, Kenji Sonomoto
    • Journal Title

      ACS Chem. Biol.

      Volume: 8 Issue: 4 Pages: 804-811

    • DOI

      10.1021/cb300717f

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-throughput screening of inhibitors targeting Agr/Fsr quorum sensing in Staphylococcus aureus and Enterococcus faecalis2013

    • Author(s)
      Desouky SE, Nishiguchi K, Zendo T, Igarashi Y, Williams P, Sonomoto K, Nakayama J.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 77 Pages: 923-927

    • NAID

      10031177575

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a peptide antagonist against fsr quorum sensing of Enterococcus faecalis2013

    • Author(s)
      Nakayama J, Yokohata R, Sato M, Suzuki T, Matsufuji T, Nishiguchi K, Kawai T, Yamanaka Y, Nagata K, Tanokura M, Sonomolo K
    • Journal Title

      ACS chemical biology

      Volume: (in press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide inhibitor siamycin l revealed through synchrotron radiation circular dichroism2013

    • Author(s)
      Phillips-Jones MK, Patching SG, Edara S, Nakayama J, Hussain R, Siligardi G.
    • Journal Title

      Phys Chem Chem Phys

      Volume: 15 Issue: 2 Pages: 444-447

    • DOI

      10.1039/c2cp43722h

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interactions of the intact FsrC membrane histidine kinase with its pheromone ligand GBAP revealed through synchrotron radiation circular dichroism2012

    • Author(s)
      Patching SG, Edara S, Ma P, Nakayama J, Hussain R, Siligardi G, Phillps-Jones MK
    • Journal Title

      Biochim Biophys Acta

      Volume: 1818 Pages: 1595-1602

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The incongruent gelatinase genotype and phenotype in Enterococcus faecalis are due to shutting off the ability to respond to the gelatinase biosynthesis-activating pheromone (GBAP) quorum-sensing signal2011

    • Author(s)
      N.Teixeira, S.Santos, P.Marujo, R.Yokohata, V.S.Iyer, J.Nakayama, L.E.Hancock, P.Serror, M.de F.S.Lopes
    • Journal Title

      Microbiology

      Volume: 158 Issue: 2 Pages: 519-528

    • DOI

      10.1099/mic.0.055574-0

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 放線菌の生産する環状デプシペプチドによるクオラムセンシング阻害作用機構の解明2014

    • Author(s)
      庄島あかね、松藤貴久、Said E. Desouky、大久保謙一、Ravindra Pal Singh、清水 徹、大谷 郁、五十嵐康弘、園元謙二、中山二郎
    • Organizer
      第21回生物工学会九州支部熊本大会
    • Place of Presentation
      熊本大学工学部
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] ウェルシュ菌における内在性クオラムクエンチング誘導物質の精製2014

    • Author(s)
      河野通生、大谷 郁、Ravindra Pal Singh、石橋直樹、園元謙二、清水 徹、中山二郎
    • Organizer
      第21回生物工学会九州支部熊本大会
    • Place of Presentation
      熊本大学工学部
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of autoinducing peptide of Clostridium perfringens and development of its inhibitors2014

    • Author(s)
      Ravindra Pal Singh, Kaori Ohtani, Ryoji Yokohata, Kenji Sonomoto, Toru Shimizu, Jiro Nakayama
    • Organizer
      5th ASM conference on cell-cell communicaion in bacteria
    • Place of Presentation
      San Antonio
    • Year and Date
      2014-10-18 – 2014-10-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 放線菌の生産する環状デプシペプチドによるクオラムセンシング阻害活性2014

    • Author(s)
      庄島あかね, 松藤貴久, Desouky Said Elsayed,大久保謙一,五十嵐康弘,園元謙二,中山二郎
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      明治大学生田キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] Hamigera 属糸状菌が生産するクオラムセンシング阻害物質に関する研究2014

    • Author(s)
      門嶋泰斗, 郷田史也, 花房知朗, 松藤貴久,中山二郎,五十嵐康弘
    • Organizer
      日本農芸化学会2014年度大会
    • Place of Presentation
      明治大学生田キャンパス
    • Related Report
      2013 Annual Research Report
  • [Presentation] グラム陽性日和見感染菌のクオラムセンシング阻害剤のスクリーニングと構造解析2013

    • Author(s)
      庄島あかね、松藤貴久、Said E. Desouky、Paul William、五十嵐康弘、園元謙二、中山二郎
    • Organizer
      第50回化学関連支部合同九州大会
    • Place of Presentation
      北九州AIMビル
    • Related Report
      2013 Annual Research Report
  • [Presentation] 微生物二次代謝産物を対象としたグラム陽性病原細菌のクオラムセンシング阻害物質の探索2013

    • Author(s)
      松藤貴久,Said Desouky,五十嵐康弘,園元謙二,中山二郎
    • Organizer
      第20回九州支部佐賀大会
    • Place of Presentation
      佐賀大学農学部
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腸球菌にクオラムセンシング阻害剤ZBzl-YAA5911の創製とその抗感梁症剤としての効果検証2012

    • Author(s)
      中山二郎, 横畑綾治, 松藤貴久, 鈴木崇, 永田宏次, 園元謙二
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2012-12-12
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸琢菌におけるGelat mase Biosynthesis Activating Pheromone (GBAP)の生合成機構解析2012

    • Author(s)
      北川はるか, 横畑綾治, 佐土原理江, 園元謙二, 中山二郎
    • Organizer
      第19回九州支部大分大会
    • Place of Presentation
      別府大学
    • Year and Date
      2012-12-01
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸球菌のクオラムセンシング阻害剤YAA5911の誘導体化と活性評価2012

    • Author(s)
      松藤貴久・横畑綾治・園兀謙二・中山二郎
    • Organizer
      第49回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report
  • [Book] Microbial Biofilms - Methods and Protocols2014

    • Author(s)
      Gianfranco Donelli, Akane Shojima, Jiro Nakayama et al.
    • Total Pages
      377
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] Quorum sensing vs Quorum quenching: A battle with no end in sight2014

    • Author(s)
      Vipin Chandra Kalia, Ravindra Pal Singh, Jiro Nakayama et al.
    • Total Pages
      391
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] MicrobialBiofilms2014

    • Author(s)
      Shojima A, Nakayama J. et al.
    • Total Pages
      380
    • Publisher
      HumanaPress
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] クロストリジウム属の菌の毒素産生抑制活性を有するペプチド2015

    • Inventor(s)
      清水徹、大谷郁、中山二郎、高橋志達、岡健太郎ら
    • Industrial Property Rights Holder
      高橋志達、岡健太郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-02-04
    • Related Report
      2014 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] クロストリジウム属の菌の毒素産生抑制活性を有するペプチド2014

    • Inventor(s)
      清水徹、大谷郁、中山二郎、高橋志達、岡健太郎ら
    • Industrial Property Rights Holder
      高橋志達、岡健太郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-10-16
    • Related Report
      2014 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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