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Preclinical trial of bacteriophage therapy against severe Pseudomonas aeruginosa pnneumoina

Research Project

Project/Area Number 18K19590
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Sawa Teiji  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10206013)

Co-Investigator(Kenkyū-buntansha) 木下 真央  京都府立医科大学, 医学(系)研究科(研究院), 助教 (20816384)
藤木 純平  酪農学園大学, 獣医学群, 講師 (30805114)
清水 優  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40800131)
岩野 英知  酪農学園大学, 獣医学群, 教授 (60382488)
Project Period (FY) 2018-06-29 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsバクテリオファージ療法 / 緑膿菌 / 重症肺炎 / 多剤耐性菌 / 三型分泌システム / 緑膿菌性肺炎 / 薬剤耐性 / グラム陰性菌 / 三型分泌毒素 / 急性肺傷害 / 抗菌療法 / ファージ療法 / 肺炎 / III型分泌システム / 動物モデル / 耐性菌 / 敗血症 / バクテリオファージ / 薬剤耐性菌 / 抗菌薬
Outline of Final Research Achievements

The utility of bacteriophage therapy for severe bacterial pneumonia was examined using an animal model of severe Pseudomonas pneumonia. In the context of global overuse of antibiotics, the spread of multidrug-resistant bacteria has become a worldwide issue, raising concerns about the emergence of superbugs such as extensively drug-resistant or pan-drug-resistant bacteria, posing a significant threat to humanity's future. Specifically, addressing multidrug-resistant Pseudomonas pneumonia in immunocompromised patients poses a social challenge. This study investigated the therapeutic efficacy and side effects of bacteriophage therapy using a mouse model of severe Pseudomonas pneumonia and found that combining bacteriophage therapy with anti-type III secretion system antibody therapy could reduce lung damage, suggesting a new treatment approach for severe Pseudomonas pneumonia. This provided foundational data for the practical application of these novel therapies.

Academic Significance and Societal Importance of the Research Achievements

多剤耐性菌が地球規模で蔓延してきている社会情勢のなかで、抗菌剤だけに頼らない重症感染症を制御する治療法開発が強く求められている。特に21世紀に入って高齢者社会は増々進行し、医療高度化に伴い抗がん剤治療や移植医療などに起因する医原性免疫不全状態にある患者も増加し、重症感染症に対する新規治療法を開発することが喫緊の課題である。そこで、バクテリオファージ療法が細菌の薬剤耐性に対処する新たな代替治療法の一つとして検討がはじまっている。多剤耐性菌に対する新戦略として可能性を持つバクテリオファージ療法について、実用化に向けて動物実験で有効性を示せたことは、実用化に向けて意義深い研究成果が得られたと考える。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (34 results)

All 2024 2023 2022 2021 2020 2019 2018 Other

All Journal Article (19 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (11 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Immunological response to subcutaneous and intranasal administration of SARS-CoV-2 spike protein in mice.2024

    • Author(s)
      Kinoshita M, Muranishi K, Kawaguchi K, Sudo K, Inoue K, Ishikura H, Sawa T
    • Journal Title

      Vaccines

      Volume: 12 Issue: 4 Pages: 343-343

    • DOI

      10.3390/vaccines12040343

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of acute lung injury assessed by chest computed tomography, oxygen saturation/fraction of inspired oxygen ratio, and serum lactate dehydrogenase in patients with COVID-192024

    • Author(s)
      Matsubara Shin、Sudo Kazuki、Kushimoto Kohsuke、Yoshii Ryogo、Inoue Keita、Kinoshita Mao、Kooguchi Kunihiko、Shikata Satoru、Inaba Tohru、Sawa Teiji
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 30 Issue: 5 Pages: 406-416

    • DOI

      10.1016/j.jiac.2023.11.013

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪心・嘔吐の細胞レベルでの起源.2024

    • Author(s)
      佐和貞治.
    • Journal Title

      麻酔

      Volume: 73 Pages: 5-10

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine2023

    • Author(s)
      Muranishi Kentaro、Kinoshita Mao、Inoue Keita、Ohara Junya、Mihara Toshihito、Sudo Kazuki、Ishii Ken J.、Sawa Teiji、Ishikura Hiroyasu
    • Journal Title

      Vaccines

      Volume: 12 Issue: 1 Pages: 5-5

    • DOI

      10.3390/vaccines12010005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choice of respiratory therapy for COVID-19 patients with acute hypoxemic respiratory failure: a retrospective case series study2023

    • Author(s)
      Sudo Kazuki、Sawa Teiji、Kushimoto Kohsuke、Yoshii Ryogo、Yuasa Kento、Inoue Keita、Kinoshita Mao、Yamasaki Masaki、Kooguchi Kunihiko
    • Journal Title

      PeerJ

      Volume: 11 Pages: e15174-e15174

    • DOI

      10.7717/peerj.15174

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of a Novel Trivalent Vaccine Formulation against Acute Lung Injury Caused by Pseudomonas aeruginosa2023

    • Author(s)
      Inoue Keita、Kinoshita Mao、Muranishi Kentaro、Ohara Junya、Sudo Kazuki、Kawaguchi Ken、Shimizu Masaru、Naito Yoshifumi、Moriyama Kiyoshi、Sawa Teiji
    • Journal Title

      Vaccines

      Volume: 11 Issue: 6 Pages: 1088-1088

    • DOI

      10.3390/vaccines11061088

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生体防御としての悪心・嘔吐とその進化学的意義. 嘔気が関わる線虫からの知見:ミトコンドリアストレスと統合的ストレス応答.2023

    • Author(s)
      佐和貞治
    • Journal Title

      Anet

      Volume: 27 Pages: 3-9

    • Related Report
      2023 Annual Research Report
  • [Journal Article] 緑膿菌ワクチンの可能性.2023

    • Author(s)
      佐和貞治,川口顕,須藤和樹,小原潤也,井上敬太,木下真央,内藤慶史.
    • Journal Title

      呼吸器内科

      Volume: 43 Pages: 440-446

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Adverse reactions to the first and second doses of Pfizer-BioNTech COVID-19 vaccine among healthcare workers.2022

    • Author(s)
      Maruyama A, Sawa T, Teramukai S, Katoh N.
    • Journal Title

      J Infect Chemothe

      Volume: Mar 25 Issue: 7 Pages: 934-942

    • DOI

      10.1016/j.jiac.2022.03.015

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difficult Airway Management in Neonates and Infants: Knowledge of Devices and a Device-Oriented Strategy2021

    • Author(s)
      Sawa Teiji、Kainuma Atsushi、Akiyama Koichi、Kinoshita Mao、Shibasaki Masayuki
    • Journal Title

      Frontiers in Pediatrics

      Volume: 9 Pages: 654291-654291

    • DOI

      10.3389/fped.2021.654291

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Power spectrum and spectrogram of EEG analysis during general anesthesia: Python-based computer programming analysis.2021

    • Author(s)
      Sawa T, Yamada T, Obata Y
    • Journal Title

      J Clin Monit Comput

      Volume: Oct 29 Issue: 3 Pages: 1-1

    • DOI

      10.1007/s10877-021-00771-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidemiological survey of serum titers from adults against various Gram-negative bacterial V-antigens.2020

    • Author(s)
      Kinoshita M, Shimizu M, Akiyama K, Kato H, Moriyama K, Sawa T.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 3 Pages: 15-15

    • DOI

      10.1371/journal.pone.0220924

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance.2020

    • Author(s)
      Sawa T, Kooguchi K, Moriyama K.
    • Journal Title

      J Intensive Care

      Volume: 28 Issue: 1 Pages: 13-13

    • DOI

      10.1186/s40560-020-0429-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular epidemiology of clinically high-risk Pseudomonas aeruginosa strains: Practical overview.2020

    • Author(s)
      Sawa T, Momiyama K, Mihara
    • Journal Title

      Microbiol Immunol

      Volume: - Issue: 5 Pages: 1-1

    • DOI

      10.1111/1348-0421.12776

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secondary in-hospital epidemiological investigation after an outbreak of Pseudomonas aeruginosa ST3572020

    • Author(s)
      Mihara T, Kimura T, Momiyama K, Kainuma A, Akiyama K, Ohara J, Inoue K, Kinoshita M, Shimizu M, Moriyama K, Fujita N, Sawa T.
    • Journal Title

      J Infect Chemother

      Volume: 26 Issue: 3 Pages: 257-265

    • DOI

      10.1016/j.jiac.2019.09.014

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunoglobulin for Treating Bacterial Infections: One More Mechanism of Action. Development of Therapeutic Antibodies against Toxins and Pathogens.2019

    • Author(s)
      Sawa T, Kinoshita M, Inoue K, Ohara J, Moriyama K.
    • Journal Title

      Antibodies

      Volume: 8 Issue: 4 Pages: 52-52

    • DOI

      10.3390/antib8040052

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The protective effects of nasal PcrV-CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia.2018

    • Author(s)
      Naito Y, Hamaoka S, Kinoshita M, Kainuma A, Shimizu M, Katoh H, Moriyama K, Ishii KJ, Sawa T.
    • Journal Title

      Microbiol Immunol

      Volume: 62 Pages: 774-785

    • NAID

      40021778113

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] An outbreak of fluoroquinolone-resistant Pseudomonas aeruginosa ST357 harboring the exoU gene.2018

    • Author(s)
      Kainuma A, Momiyama K, Kimura T, Akiyama K, Inoue K, Naito Y, Kinoshita M, Shimizu M, Kato H, Shime N, Fujita N, Sawa T.
    • Journal Title

      J Infect Chemother.

      Volume: in press Issue: 8 Pages: 615-622

    • DOI

      10.1016/j.jiac.2018.03.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 多剤耐性緑膿菌に対する免疫療法.2018

    • Author(s)
      内藤慶史、佐和貞治.
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 444-449

    • Related Report
      2018 Research-status Report
  • [Presentation] Development of EEG mode decompositor:Hilbert spectrum analysis of electroencephalography durng geenral anesthesia by modified empirical wavelet transform (wavelet mode decomposition).2023

    • Author(s)
      Sawa T, Sudo K, Obata Y, Akiyama K
    • Organizer
      Annual Meeting of International Anesthesia Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Statistical causal inferences involving respiratory management in COVID-19 severe respiratory failure: a retrospective-single center cohort study.2023

    • Author(s)
      Sudo K, Sawa T, Kushimoto K, Yoshii R, Yuasa K, Inoue K, Kinoshita M, Yamasaki M, Kooguchi K.
    • Organizer
      Annual Meeting of International Anesthesia Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical research for decision making in the initiation of mechanical ventilation therapy using ROX index and chest CT images in COVID-19 patients; Single-center retrospective cohort study.2022

    • Author(s)
      Sudo K, Kinoshita M, Kento K, Inoue K, Ohara J, Muranishi K, Sawa T.
    • Organizer
      The 22nd KSCCM-JSICM Joint Congress.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] ランスレーショナル・リサーチ 細菌感染と急性肺傷害2022

    • Author(s)
      佐和貞治
    • Organizer
      第42回日本臨床麻酔学会大会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] COVID-19重症呼吸不全の呼吸療法選択に関与する因子についての因果推論ベイジアンネットワーク解析2022

    • Author(s)
      須藤和樹, 湯浅健人, 串本洸輔, 吉井龍吾, 井上敬太, 山崎正記, 木下真央, 小尾口邦彦,佐和貞治.
    • Organizer
      4大学連携研究フォーラム
    • Related Report
      2022 Research-status Report
  • [Presentation] COVID-19重症患者での人工呼吸管理/高流量経鼻酸素療法選択の統計学的因果推論ネットワーク解析.2022

    • Author(s)
      須藤和樹, 湯浅健人, 吉井龍吾, 井上敬太, 山崎正記, 小尾口邦彦, 佐和貞治
    • Organizer
      第40回日本麻酔・集中治療テクノロジー学会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] バクテリオファージと PcrV 抗体の治療効果の検討2022

    • Author(s)
      小原潤也、藤木純平 、木下真央 、井上敬太 、須藤和樹、湯浅健人、岩野英知、佐和貞治
    • Organizer
      第56回緑膿菌感染症研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] シンポジウム. 緑膿菌に学び, 緑膿菌を操る . タイプ III 毒素分泌機構2020

    • Author(s)
      佐和貞治
    • Organizer
      第94回日本感染症学会学術講演会, 2020年8月東京.
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Frequency analysis-linked Poincare plot-integrated score (f-PIS) of the electroencephalogram during general anesthesia.2018

    • Author(s)
      Sawa T, Hayashi K, Kainuma A, Inoue K, Kinoshita M.
    • Organizer
      IARS 2018. Annual Meeting and International Science Symposium. International Anesthesia Research Society.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Arterial pulse waveform analysis.2018

    • Author(s)
      Sawa T. Experience exchange session.
    • Organizer
      Experience exchange session. Edwards Life Science Limited,
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 緑膿菌毒素に対する免疫グロブリン新知見.2018

    • Author(s)
      佐和貞治.
    • Organizer
      鹿児島県薬剤師会講演会.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] TLR9リガンド添加緑膿菌V抗原ワクチンによる粘膜免疫誘導の検討. 第52回緑膿菌感染症研究会公演記録2018

    • Author(s)
      内藤慶史、濱岡早枝子、井上敬太、甲斐沼篤、石井健、佐和貞治.
    • Total Pages
      3
    • Publisher
      日本緑膿菌感染症研究会
    • Related Report
      2018 Research-status Report
  • [Book] 診断と治療社2018

    • Author(s)
      木下真央、佐和貞治.
    • Total Pages
      6
    • Publisher
      麻酔科研修ノート 改訂第3版. 感染症.
    • ISBN
      9784787824011
    • Related Report
      2018 Research-status Report
  • [Book] Construction of a recombinant single-chain antibody fragment against bacterial type III secretion. Antibody Engineering,2018

    • Author(s)
      Sawa T, Kainuma A, Moriyama K, Naito Y.
    • Total Pages
      15
    • Publisher
      InTech
    • Related Report
      2018 Research-status Report
  • [Remarks] 京都府立医科大学麻酔科学教室 佐和貞治

    • URL

      http://www.f.kpu-m.ac.jp/k/anesth/index.php?TeijiSawa

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-07-25   Modified: 2025-01-30  

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