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Establishment of a screening system for therapeutically effective antibiotics

Research Project

Project/Area Number 24689008
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Environmental pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

HAMAMOTO Hiroshi  東京大学, 薬学研究科(研究院), 助教 (90361609)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2012: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Keywords感染症 / 微生物 / 抗生物質 / カイコ / 次世代シークセンサー
Outline of Final Research Achievements

Primary mechanistic analysis of lysocin E, identified using a silkworm infection model was performed. In addition, the serum factors that enhances antimicrobial activity of lysocin E were purified and identified. Moreover, serum from various animals including human and silkworm hemolymph also enhanced antimicrobial activity of lysocin E. Further, a method was established to analyze comprehensive gene expression of bacteria during infection in mouse organs. Disruption of genes, whose functions are not known, showed reduced pathogenicity in mouse systemic infection model. These results suggested that a principle of a screening system for therapeutically effective antibiotics was established.

Report

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

    (46 results)

All 2015 2014 2013 2012 Other

All Journal Article (19 results) (of which Peer Reviewed: 16 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (23 results) (of which Invited: 7 results) Remarks (4 results)

  • [Journal Article] A novel mutation in the vraS gene of Staphylococcus aureus contributes to daptomycin resistance2015

    • Author(s)
      Su J, Iehara M, Yasukawa J, Matsumoto Y, Hamamoto H, Sekimizu K
    • Journal Title

      J Antibiot (Tokyo)

      Volume: 印刷中 Issue: 10 Pages: 646-648

    • DOI

      10.1038/ja.2015.42

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PARALYTIC PEPTIDE: AN INSECT CYTOKINE THAT MEDIATES INNATE IMMUNITY2015

    • Author(s)
      Ishii K, Hamamoto H, Sekimizu K.
    • Journal Title

      Archives of Insect Biochemistry and Physiology

      Volume: 88 Issue: 1 Pages: 18

    • DOI

      10.1002/arch.21215

    • URL

      https://pure.teikyo.jp/en/publications/4a4067d1-95c0-465a-aa04-1d8f8b309618

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane2015

    • Author(s)
      Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, Kaji T, Kuranaga T, Hamase K, Katsu T, Su J, Adachi T, Uchida R, Tomoda H, Yamada M, Souma M, Kurihara H, Inoue M, Sekimizu K.
    • Journal Title

      Nature Chemical Biology

      Volume: 11 Issue: 2 Pages: 127

    • DOI

      10.1038/nchembio.1710

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Total synthesis and biological evaluation of the antibiotic lysocin E and its enantiomeric, epimeric, and N-demethylated analogues2015

    • Author(s)
      Murai M, Kaji T, Kuranaga T, Hamamoto H, Sekimizu K, and Inoue M
    • Journal Title

      Angew. Chem. Int. Ed Engl

      Volume: 54 Issue: 5 Pages: 1556

    • DOI

      10.1002/anie.201410270

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of virulence gene expression in Staphylococcus aureus by pulmonary surfactant2014

    • Author(s)
      Ishii K, Adachi T, Yasukawa J, Suzuki Y, Hamamoto H, Sekimizu K.
    • Journal Title

      Infection and immunity

      Volume: 82 Issue: 4 Pages: 1500

    • DOI

      10.1128/iai.01635-13

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>In vitro</i> and <i>in vivo</i> anti-MRSA activities of nosokomycins2014

    • Author(s)
      Uchida R, Hanaki H, Matsui H, Hamamoto H, Sekimizu K, Iwatsuki M, Kim YP, Tomoda H
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 8 Issue: 6 Pages: 249-254

    • DOI

      10.5582/ddt.2014.01050

    • NAID

      130005054796

    • ISSN
      1881-7831, 1881-784X
    • URL

      https://pure.teikyo.jp/en/publications/d04fed37-5dae-413c-8a4f-dfd32273c4de

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] カイコをモデル動物とした創薬研究展開2014

    • Author(s)
      浜本洋
    • Journal Title

      JATAFFジャーナル

      Volume: 2 Pages: 38-43

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Silkworm as a model animal for drug development2014

    • Author(s)
      浜本洋、関水和久
    • Journal Title

      生化学

      Volume: 86 Pages: 578-582

    • NAID

      40020254204

    • Related Report
      2014 Annual Research Report
  • [Journal Article] カイコを用いた創薬研究2014

    • Author(s)
      松本靖彦、浜本洋、西田智、関水和久
    • Journal Title

      生体の科学

      Volume: 65 Pages: 613-620

    • NAID

      40020290149

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Establishment of a bacterial infection model using the European honeybee, Apis mellifera L.2014

    • Author(s)
      Ishii K, Hamamoto H, Sekimizu K.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 2 Pages: e89917-e89917

    • DOI

      10.1371/journal.pone.0089917

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a Serratia marcescens virulence factor that promotes hemolymph bleeding in the silkworm, Bombyx mori2014

    • Author(s)
      Ishii K, Adachi T, Hara T, Hamamoto H, Sekimizu K.
    • Journal Title

      Journal of Invertebrate Pathology

      Volume: 117 Issue: 1 Pages: 61

    • DOI

      10.1016/j.jip.2014.02.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells2014

    • Author(s)
      Ishii K, Adachi T, Hamarrioto H, Sekimizu K.
    • Journal Title

      Journal of Biological Chemistry.

      Volume: 289 Issue: 9 Pages: 5876

    • DOI

      10.1074/jbc.m113.544536

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-activity relationship study of novel iminothiadiazolo- pyrimidinone antimicrobial agents2013

    • Author(s)
      Paudel A, Kaneko K, Watanabe A, Shigeki M, Motomu K, Hamamoto H, Sekimizu K.
    • Journal Title

      J Antibiot (Tokyo).

      Volume: 66 Issue: 11 Pages: 663

    • DOI

      10.1038/ja.2013.69

    • URL

      https://pure.teikyo.jp/en/publications/ffa0d106-23b9-46b8-9df6-7c92a7d7de25

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antimicrobial action mechanism of flavonoids from <i>Dorstenia </i>species2013

    • Author(s)
      Dzoyem JP, Hamamoto H, Ngameni B, Ngadjui BT, Sekimizu K
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 7 Issue: 2 Pages: 66-72

    • DOI

      10.5582/ddt.2013.v7.2.66

    • NAID

      130004588093

    • ISSN
      1881-7831, 1881-784X
    • URL

      https://pure.teikyo.jp/en/publications/d39db245-5848-4fcb-862c-a76427aaef7d

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insect cytokine paralytic peptide activates innate immunity via nitric oxide production in the silkworm Bombyx mori2013

    • Author(s)
      Ishii K, Adachi T, Hamamoto H, Oonishi T, Kamimura M, Imamura K, Sekimizu K.
    • Journal Title

      Dev Comp Immunol.

      Volume: 39 Issue: 3 Pages: 147

    • DOI

      10.1016/j.dci.2012.10.014

    • URL

      https://pure.teikyo.jp/en/publications/e39dfff5-ebd2-49fd-8f2e-60848cbc56ae

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serratia marcescens induces apoptotic cell death in host immune cells via a lipopolysaccharide- and flagella-dependent mechanism2012

    • Author(s)
      Kenichi Ishii, et al.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Issue: 43 Pages: 36582

    • DOI

      10.1074/jbc.m112.399667

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of innate immune stimulating activity of polysaccharides using a silkworm (<i>Bombyx mori</i>) muscle contraction assay2012

    • Author(s)
      Fujiyuki T
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 6 Issue: 2 Pages: 88-93

    • DOI

      10.5582/ddt.2012.v6.2.88

    • NAID

      130005054745

    • ISSN
      1881-7831, 1881-784X
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide O-antigen of enterohemorrhagic Escherichia coli O157:H7 is required for killing both insects and mammals2012

    • Author(s)
      Atsushi Miyashita, et al.
    • Journal Title

      FEMS Microbiology Letters

      Volume: 333 Issue: 1 Pages: 59

    • DOI

      10.1111/j.1574-6968.2012.02599.x

    • URL

      https://pure.teikyo.jp/en/publications/cbf7586d-87d8-4c20-971f-26cfd07e9a06

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Animal welfare and use of silkworm as a model animal2012

    • Author(s)
      Nobukazu Sekimizu, Atmika Paudel, Hiroshi Hamamoto
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 6 Issue: 4 Pages: 226-229

    • DOI

      10.5582/ddt.2012.v6.4.226

    • NAID

      130005054754

    • ISSN
      1881-7831, 1881-784X
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] カイコの感染モデルを利用した新規抗生物質ライソシンの発見2015

    • Author(s)
      関水和久、浜本洋
    • Organizer
      第88回 日本細菌学会総会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] カイコモデルを用いた治療効果を有する新規抗菌薬の同定と開発2015

    • Author(s)
      浜本洋、石井健一、安川淳一朗、西田智、関水和久
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学園大学(兵庫県神戸市)
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Comprehensive gene expression analysis for Staphylococcus aureus infected in kidney2015

    • Author(s)
      Hiroshi Hamamoto, Suguru Ohgi, Yutaka Suzuki, Kazuhisa Sekimizu
    • Organizer
      International Symposium on Genome Science 2015 “Expanding Frontiers of Genome Science II
    • Place of Presentation
      一ツ橋ホール(東京都千代田区)
    • Year and Date
      2015-01-20 – 2015-01-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 宿主因子による抗生物質カイコシンの抗菌活性の促進2014

    • Author(s)
      浜本洋、安川淳一朗、石井健一、Su Jie、Paudel Atmika、関水和久
    • Organizer
      第36回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      徳島大学(徳島県徳島市)
    • Year and Date
      2014-11-20 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規抗生物質カイコシンEの治療効果の基礎となる分子メカニズム2014

    • Author(s)
      安川淳一朗、浜本洋、Su Jie、Paudel Atmika、浦井誠、西田智、関水和久
    • Organizer
      第87回生化学会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 宿主因子による新規抗生物質カイコシンE の抗菌活性の増強2014

    • Author(s)
      浜本洋、安川淳一朗、石井健一、Su Jie、Paudel Atmika、関水和久
    • Organizer
      第26回微生物シンポジウム
    • Place of Presentation
      都センターホテル、東京
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Host factors enhance the antimicrobial activity of a novel antibiotics kaikosin E2014

    • Author(s)
      Hiroshi Hamamoto, Su Jie, Atmika Paudel, Kenichi Ishii, Jyunichiro Yasukawa, Kazuhisa Sekimizu
    • Organizer
      The 54th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • Place of Presentation
      Washington(USA)
    • Year and Date
      2014-09-05 – 2014-09-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Silkworm as an animal model for novel antibiotic development2014

    • Author(s)
      Hiroshi Hamamoto, Jyunichiro Yasukawa, Kenich Ishii, Atmika Paudel, Kazuhisa Sekimizu
    • Organizer
      the Xth European Congress of Entomology
    • Place of Presentation
      York(England)
    • Year and Date
      2014-08-03 – 2014-08-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 治療効果を指向した新規抗生物質の開発に向けて2014

    • Author(s)
      浜本洋
    • Organizer
      文部科学省科学研究費新学術領域研究「ゲノム支援」公開シンポジウム
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 新規抗生物質カイコシンの作用機序と宿主因子による活性化2014

    • Author(s)
      浜本洋、安川淳一朗、石井健一、安達達朗、関水和久
    • Organizer
      日本薬学会 第134年会
    • Place of Presentation
      熊本大学(熊本県熊本市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] カイコ病態モデルを利用した医薬品の探索研究2013

    • Author(s)
      浜本洋、石川繭子、瀬筒秀樹、坪田拓也、片岡啓子、松本靖彦、垣内力、関水和久
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      横浜市(招待講演)
    • Year and Date
      2013-03-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] Characterization and mechanistic analysis of novel antibiotics Kaikosin, produced by Lysobacter sp.2013

    • Author(s)
      Hiroshi Hamamoto, Su Jie, Paudel Atomika, Makoto Urai, Kazuhisa Sekimizu
    • Organizer
      International Symposium on Genome Science Expanding Frontiers of Genome Science
    • Place of Presentation
      東京都
    • Year and Date
      2013-01-09
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular Target analysis of Novel Antibiotics Kaikosins2013

    • Author(s)
      H. HAMAMOTO, J. Su, A. PAUDEL, M. URAI, K. KATAOKA, K. SEKIMIZU
    • Organizer
      53th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
    • Place of Presentation
      USA (Denver)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Antibacterial activity of a novel lipopeptide antibiotic, kaikosin E, is enhanced by host factors2013

    • Author(s)
      J. Yasukawa, H. Hamamoto, J. Su, Paudel A, M. Urai, S. Nishida, K. Sekimizu
    • Organizer
      The 2nd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular Target analysis of the Novel Antibiotics Kaikosins2013

    • Author(s)
      K Sekimizu, H Hamamoto
    • Organizer
      The 2nd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] カイコ細菌感染モデルを用いた治療有効な新規抗生物質カイコシンの作用機序解析2013

    • Author(s)
      安川淳一朗、浜本洋、Jie Su、Atmika Paudel、浦井誠、石井健一、安達達朗、西田智、関水和久
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規抗視物質カイコシンの作用機序解析2013

    • Author(s)
      浜本洋、Su Jie、Atmika Paudel、西田智、関水和久
    • Organizer
      第25回微生物シンポジウム
    • Place of Presentation
      静岡県立大学(静岡県静岡市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規抗生物質カイコシンによる新規細胞膜破壊メカニズム2013

    • Author(s)
      安川淳一朗、浜本洋、Jie Su、Atmika Paudel、浦井誠、石井健一、安達健朗、西田智、関水和久
    • Organizer
      第35回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      東京大学(東京都文京区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 次世代シークエンサーを用いた黄色ブドウ球菌の宿主応答因子の網羅的な解析手法2013

    • Author(s)
      浜本洋、石井健一、安達健朗、鈴木穣、関水和久
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアホテル(兵庫県神戸市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] カイコ病態モデルを利用した医薬品の探索研究2013

    • Author(s)
      浜本洋
    • Organizer
      日本動物実験代替法学会第26回大会
    • Place of Presentation
      京都テレサ(京都府京都市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 新規抗生物質カイコシンの作用機序解析に関する研究2012

    • Author(s)
      浜本洋、Su Jie、Atmika Paudel、浦井誠、片岡啓子、関水和久
    • Organizer
      第34回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      京都府
    • Year and Date
      2012-11-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Purification of a serum factor enhancing Kaikosin E activity against Staphylococcus aureus2012

    • Author(s)
      Su Jie, Hiroshi Hamamoto, Kazuhisa Sekimizu
    • Organizer
      The 1st International Symposium on Chemical Biology of Natural Products : Target ID and Regulation of Bioactivity
    • Place of Presentation
      東京都
    • Year and Date
      2012-10-31
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規環状リポペプチド系抗生物質カイコシンの作用機序解析2012

    • Author(s)
      浜本洋、Su Jie、浦井誠、Atmika Paudel、片岡啓子、関水和久
    • Organizer
      第24回微生物シンポジウム
    • Place of Presentation
      大阪府
    • Year and Date
      2012-09-04
    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京大学大学院薬学系研究科微生物薬品化学教室のホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~bisei/research_hamamoto.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 記者会見 「新規作用機序を有する抗生物質ライソシンの発見 カイコを利用した実験から」

    • URL

      http://www.u-tokyo.ac.jp/public/public01_261209_j.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 浜本助教の研究テーマ

    • URL

      http://www.f.u-tokyo.ac.jp/~bisei/research_hamamoto.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.f.u-tokyo.ac.jp/~bisei/research_hamamoto.html

    • Related Report
      2012 Annual Research Report

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

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