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Establishment of antibody-cocktail therapy against invading bacteria for sepsis patients

Research Project

Project/Area Number 18K08868
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionTokai University

Principal Investigator

Watanabe Nobuo  東海大学, 医学部, 助教 (80396928)

Co-Investigator(Kenkyū-buntansha) 井上 茂亮  東海大学, 医学部, 准教授 (30582209)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsモノクローナル抗体 / 感染症 / 薬剤耐性 / 活性抗体 / 膜タンパク質 / 抗菌活性 / ペプチドグリカン / クオラムセンシング / 多剤耐性菌 / MRSA / 感染菌 / 抗体
Outline of Final Research Achievements

Establishment of a therapeutic strategy against infectious diseases caused by drug-resistant bacteria including Methicillin-Resistant Staphylococcus aureus (MRSA) is a long-standing challenge; however, almost no antibody to MRSA has successfully showed effectiveness in the clinical trials. In this study, we targeted 2 master proteins responsible for toxin synthesis and 3 key proteins responsible for cell wall biosynthesis, respectively, and generated a total of 25 monoclonal antibodies in mice. Unfortunately, however, none of them demonstrated expected anti-MRSA activity on its own. However, now it has become possible to assess the anti-MRSA effect of these antibodies in combination with other antibodies and antibiotics etc.

Academic Significance and Societal Importance of the Research Achievements

本研究において作製した抗MRSA抗体はいずれも単独では当初期待した効果(抗毒素産生作用ならびに抗増殖作用)は見られなかった。しかしこの結果、5種のタンパク質に関しては、今後の標的とすべき配列が絞り込まれたことになる。また、今後は他の抗体ならびに各種の抗菌剤との併用効果を検証しすることによって付加的な抗菌効果が得られるか検討する予定である。ハイブリドーマは樹立され液体窒素に保管されているため、必要に応じてすぐに抗体の追加産生ならびにヒト化抗体化が可能である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results)

  • [Journal Article] Usefulness of next-generation DNA sequencing for the diagnosis of urinary tract infection2020

    • Author(s)
      Ishihara T, Watanabe N, Inoue S, Aoki H, Tsuji T, Yamamoto B, Yanagi H, Oki M1, Kryukov K, Nakagawa S, Inokuchi S, Ozawa H, Imanishi T
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 14 Issue: 1 Pages: 42-49

    • DOI

      10.5582/ddt.2020.01000

    • NAID

      130007802636

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2020-02-29
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Podoplanin is indispensable for cell motility and platelet-induced epithelial-to-mesenchymal transition-related gene expression in esophagus squamous carcinoma TE11A cells2020

    • Author(s)
      Watanabe N, Kidokoro M, Tanaka M, Inoue S, Tsuji T, Akatuska H, Okada C, Iida Y, Okada Y, Suzuki Y, Sato T, Yahata T, Hirayama N, Nakagawa Y, Inokuchi S.
    • Journal Title

      Cancer Cell International

      Volume: 20 Issue: 1 Pages: 263-263

    • DOI

      10.1186/s12935-020-01328-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A pull-down and slot blot-based screening system for inhibitor compounds of the podoplanin-CLEC-2 interaction2019

    • Author(s)
      Watanabe N, Kidokoro M, Suzuki Y, Tanaka M, Inoue S, Tsukamoto H, Hirayama N, Hsieh PW, Tseng CP, Nakagawa Y, Inokuchi S
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 9 Pages: e0222331-e0222331

    • DOI

      10.1371/journal.pone.0222331

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Papaverine identified as an inhibitor of high mobility group box 1/receptor for advanced glycation end-products interaction suppresses high mobility group box 1-mediated inflammatory responses.2019

    • Author(s)
      Tamada K, Nakajima S, Ogawa N, Inada M, Shibasaki H, Sato A, Takasawa R, Yoshimori A, Suzuki Y, Watanabe N, Oyama T, Abe H, Inoue S, Abe T, Yokomizo T, Tanuma S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 511 Issue: 3 Pages: 665-670

    • DOI

      10.1016/j.bbrc.2019.01.136

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of pathogenic bacteria in the blood from sepsis patients using 16S rRNA gene amplicon sequencing analysis.2018

    • Author(s)
      Watanabe N, Kryukov K, Nakagawa S, Takeuchi JS, Takeshita M, Kirimura Y, Mitsuhashi S, Ishihara T, Aoki H, Inokuchi S, Imanishi T, Inoue S
    • Journal Title

      PLoS One

      Volume: 13 Issue: 8 Pages: e0202049-e0202049

    • DOI

      10.1371/journal.pone.0202049

    • NAID

      120006826803

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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