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Studies on the next-generation antimicrobial agents by high-through-put screening of small-molecule compounds inhibiting bacterial effector

Research Project

Project/Area Number 25670208
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionChiba University

Principal Investigator

TOMOKO Yamamoto  千葉大学, 薬学研究科(研究院), 教授 (60110342)

Co-Investigator(Kenkyū-buntansha) TAKAYA Akiko  千葉大学, 大学院薬学研究院, 准教授 (80334217)
SATO Yoshiharu  千葉大学, 大学院薬学研究院, 助教 (00554586)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords抗感染症薬 / 薬剤耐性 / エフェクター / E3リガーゼ / 阻害剤 / 次世代抗感染症薬 / 病原性 / E3リガーゼ / 次世代型抗感染症薬
Outline of Final Research Achievements

Antimicrobial resistance threatens the effective prevention and treatment of bacterial infections. However, the increasing understanding of bacterial pathogenesis has revealed many potential strategies to combat bacteria-mediated diseases. Bacterial effectors are involved in establishing disease processes, but those are not essential for bacterial growth or homeostasis. Thus, effector is expected to be a candidate of therapeutic target, and inhibitors of effectors could potentially reduce virulence without causing bacterial death, thereby avoiding any subsequent development of resistance. In this study, we performed to isolate small-molecule inhibitors of Salmonella effector, SrlP by conducting high-through-put screening by exploiting the library deposited by Chiba University. We have also revealed that the molecule targeted by SspH2 is in the cytoplasm of macrophage cells.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 Other

All Journal Article (14 results) (of which Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Invited: 1 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Molecular characterization of linezolid-resistant CoNS isolates in Japan.2015

    • Author(s)
      Takaya A, Kimura A, Sato Y, Ishiwada N, Watanabe M, Matsui M, Shibayama K, Yamamoto T.
    • Journal Title

      J. Atimicrob. Chemother.

      Volume: 70 Issue: 3 Pages: 658-663

    • DOI

      10.1093/jac/dku443

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mouse models assessing the crossptotective efficacy of oral non-typhoidal Salmonella vaccine candidates harboring in-frame deletions of the ATPdependent protease Lon and other genes.2015

    • Author(s)
      Matsui H., Fukiya S., Kodama-Akaboshi C., Eguchi M. and Yamamoto T.
    • Journal Title

      J. Med. Microbiol.

      Volume: 64 Issue: 3 Pages: 295-302

    • DOI

      10.1099/jmm.0.000014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FliT selectively enhances proteolysis of FlhC subunit in FlhD4C2 complex by an ATP-dependent protease ClpXP.2014

    • Author(s)
      Sato Y, Takaya A, Mouslim C, Hughes K.T., Yamamoto T.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 47 Pages: 33001-33011

    • DOI

      10.1074/jbc.m114.593749

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] サルモネラマクロファージ感染におけるカスパーゼ-8活性制御2014

    • Author(s)
      高屋明子、山本友子
    • Journal Title

      感染・炎症・免疫

      Volume: 44 Pages: 53-64

    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] 細菌の進化から考える抗菌薬耐性:マクロライド耐性.2014

    • Author(s)
      山本友子
    • Journal Title

      化学療法の領域

      Volume: 30 Pages: 44-54

    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] Evolutionary model of the divergence of enterohemorrhagic Escherichia coli O157 lineage I/II clades reconstructed from high resolution melting and Shiga-like toxin 2 analyses2014

    • Author(s)
      Etoh Y, Hirai S, Ichihara S, Maeda E, Yokoyama E, Sera N, Horikawa K, Yamamoto T.
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 24 Pages: 140

    • DOI

      10.1016/j.meegid.2014.03.013

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the population genetics of clades of enterohaemorrhagic Escherichia coli O157: H7/H- isolated in three areas in Japan2014

    • Author(s)
      Hirai S, Yokoyama E, Etoh Y, Seto J, Ichihara S, Suzuki Y, Maeda E, Sera N, Horikawa K, Yamamoto T.
    • Journal Title

      J Appl Microbiol.

      Volume: 117 Issue: 4 Pages: 1191

    • DOI

      10.1111/jam.12604

    • URL

      https://pure.teikyo.jp/en/publications/b8c23a0d-730b-4499-9d31-e75d868547b4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of a novel nicotinamide phosphoribosyl transferase (NAMPT) inhibitor via in silico screening.2014

    • Author(s)
      Takeuchi M, Niimi T, Masumoto M, Orita M, Yokota H, Yamamoto T.
    • Journal Title

      Biol.pharm.Bull.

      Volume: 37 Pages: 31-36

    • NAID

      130003382094

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] サルモネラの病原性2014

    • Author(s)
      山本 友子
    • Journal Title

      臨床と微生物

      Volume: 41 Pages: 84-89

    • Related Report
      2013 Research-status Report
  • [Journal Article] 特集・細菌の進化から考える抗菌薬耐性-マクロライド耐性2014

    • Author(s)
      山本 友子
    • Journal Title

      化学療法の領域

      Volume: 30 Pages: 44-54

    • Related Report
      2013 Research-status Report
  • [Journal Article] サルモネラ感染症の発症メカニズム2014

    • Author(s)
      高屋明子、山本友子
    • Journal Title

      感染症内科

      Volume: 2

    • Related Report
      2013 Research-status Report
  • [Journal Article] Methylation of 23S rRNA Nucleotide G748 by RlmAII Methyltransferase Renders Streptococcus pneumoniae Telithromycin Susceptible.2013

    • Author(s)
      Takaya A, Sato Y, Shoji T, Yamamoto T
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 57 Issue: 8 Pages: 3789-3796

    • DOI

      10.1128/aac.00164-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis.2013

    • Author(s)
      Sugisaki K, Hanawa T, Yonezawa H, Osaki T, Fukutomi T, Kawakami H, Yamamoto T, Kamiya S.
    • Journal Title

      Microbiology

      Volume: 159 Issue: Pt_7 Pages: 1379-1389

    • DOI

      10.1099/mic.0.066597-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Linkage disequilibrium of the IS629 insertion among different clades of enterohemorrhagic Escherichia coli O157:H7/H-strains.2013

    • Author(s)
      Hirai S, Yokoyama E, Yamamoto T.
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 18 Pages: 94-99

    • DOI

      10.1016/j.meegid.2013.05.006

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] サルモネラRNA シャペロンによるマクロファージ応答遺伝子発現制御2015

    • Author(s)
      高屋 明子,前田 侑也,佐藤 慶治,山本 友子
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜県
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] グラム陽性菌の内因性rRNA修飾と薬剤耐性2014

    • Author(s)
      高屋明子
    • Organizer
      感染症研究グローバルネットワークフォーラム2014
    • Place of Presentation
      千葉県
    • Year and Date
      2014-11-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 臨床由来コアグラーゼ陰性ブドウ球菌のリネゾリド耐性機構2014

    • Author(s)
      高屋明子、木村旭、佐藤慶治、石和田稔彦、渡辺正治、松井真理、柴山恵吾、山本友子
    • Organizer
      第43回薬剤耐性菌研究会
    • Place of Presentation
      石川県
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺炎球菌のテリスロマイシン感受性に寄与するrRNA内因性修飾2014

    • Author(s)
      庄司竜麻,高屋明子,木村聡,鈴木勉,佐藤慶治,山本友子
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-30 – 2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] マルチオミクス解析によるサルモネラエフェクター予測と分泌制御様式の理解2014

    • Author(s)
      佐藤 慶治,高屋 明子,山本 友子
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-30 – 2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genetical Assessment of Linezolid Resistance Mechanisms in Staphylococcus capitis Isolated Clinically2014

    • Author(s)
      Takaya A, Kimura A, Sato Y, Yamamoto T.
    • Organizer
      Interscience Conference on Antimicrobial Agents and Chemotherapy
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2014-09-05 – 2014-09-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] サルモネラ感染による骨髄免疫細胞の傷害2014

    • Author(s)
      日野浩介,高屋明子,佐藤慶治,常世田好司,山本友子
    • Organizer
      第8回細菌学若手コロッセウム
    • Place of Presentation
      北海道
    • Year and Date
      2014-08-06 – 2014-08-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] The function and regulation of Salmonella pathogenicity islands 1and 2 in host cells2014

    • Author(s)
      高屋 明子,佐藤 慶治,山本 友子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] FliT enhances the ClpXP-catalyzed degradation of masterregulator FlhD4C2 in Salmonella2014

    • Author(s)
      佐藤 慶治,高屋 明子,山本 友子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺炎球菌のテリスロマイシン感受性に寄与するrRNA段階的修飾2014

    • Author(s)
      庄司竜麻,高屋明子,佐藤慶治,山本友子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] リネゾリド長期投与におけるリネゾリド耐性Coagulase-negative Staphylococccusの出現と耐性化機構2013

    • Author(s)
      木村旭、高屋明子、石和田稔彦、渡邊正治、野村文夫、山本友子
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] サルモネラFliTによるClpXPプロテアーゼ依存的FlhC分解促進機構2013

    • Author(s)
      小田倉香織、佐藤慶治、高屋明子、唐田清信、山本友子
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] サルモネラ新規エフェクターSTM1239の同定2013

    • Author(s)
      松井 優里, 高屋 明子, 佐藤 慶治, 山本 友子
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] FliT fine-tunes the flagellar biogenesis by enhancing the ClpXP-catalyzed degradation of master regulator FlhD4C22013

    • Author(s)
      Yoshiharu Sato, Akiko Takaya, Tomoko Yamamoto
    • Organizer
      EMBO workshop on AAA+ proteins: from mechanism and disease to targets.
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺炎球菌リボソームとTELの相互作用におけるリボソーム内因性修飾酵素の影響2013

    • Author(s)
      庄司竜麻、高屋明子、佐藤慶治、山本友子
    • Organizer
      第7回細菌学若手コロッセウム
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
  • [Presentation] CspC/CspEによるサルモネラの病原性発現制御2013

    • Author(s)
      前田侑也、高屋明子、胡東良、岡村雅史、佐藤慶治、山本友子
    • Organizer
      第7回細菌学若手コロッセウム
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
  • [Book] みてわかる薬学 図解 微生物学・感染症・化学療法2014

    • Author(s)
      藤井暢弘、山本友子、横田伸一、花輪智子、岡崎克則、村山琮明、丸山治彦
    • Total Pages
      494
    • Publisher
      南山堂
    • Related Report
      2014 Annual Research Report
  • [Book] 病原微生物学 基礎と臨床2014

    • Author(s)
      荒川宜親、神谷茂、柳雄介、山本友子、上田啓次、江崎孝行、尾家重治、大石和徳、太田伸生、大西真、大野尚仁、川端重忠、岸本寿男、清田浩、桑野剛一、小林和夫、小柳義夫、坂口剛正、柴山恵吾、菅井基行、高月英恵、田中靖人、他
    • Total Pages
      294
    • Publisher
      東京化学同人
    • Related Report
      2014 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院 微生物薬品化学研究室ホームページ

    • URL

      http://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 千葉大院薬・微生物薬品化学研究室ホームページ

    • URL

      http://www.p.chiba-u.ac.jp/lab/bisei/

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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