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Development of CRISPR-Cas-type antibacterial agents specifically targeting MRSA

Research Project

Project/Area Number 20K21671
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionNiigata University

Principal Investigator

Terao Yutaka  新潟大学, 医歯学系, 教授 (50397717)

Co-Investigator(Kenkyū-buntansha) 伊東 孝祐  新潟大学, 自然科学系, 准教授 (20502397)
土門 久哲  新潟大学, 医歯学系, 准教授 (00594350)
前川 知樹  新潟大学, 医歯学系, 研究教授 (50625168)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
KeywordsMRSA
Outline of Research at the Start

抗菌薬に耐性を示す黄色ブドウ球菌(MRSA)が,各国で数得多くの院内感染を引き起こし問題となっている.しかしながら,耐性菌の新薬開発研究は,国内外で不十分という現実に直面している.そこで本研究では,CRISPR-Casゲノム編集技術を応用し,MRSAの耐性因子PBP2’等の遺伝子を特異的に削除するDNA製抗菌薬の開発に挑戦する.

Outline of Final Research Achievements

The estimated death by MRSA infections in Japan is more than 10,000 per year. Furthermore, in the latest infection control surveillance, the MRSA detection rate at domestic medical institutions was approximately 100%. Nevertheless, research and development of new drugs against drug-resistant bacteria is facing the reality of inadequacy. Therefore, in this present study, we applied CRISPR-Cas genome editing technology to develop a DNA antibacterial drug that specifically deletes the resistance factor PBP2' in MRSA. By using DNA (CRISPR-Cas expression plasmid) as a material, the possibility of side reactions will be low, and the drug target will be able to exchange simply by changing the guide RNA sequence according to the evolution of resistance. This was because it could be an antibacterial drug.

Academic Significance and Societal Importance of the Research Achievements

本研究では,歯科臨床にも関連深いMRSA対策を足掛りとし,成果の波及を期すのは,WHOが予測する2050年における世界の耐性菌問題である.将来の耐性菌により推計される被害,すなわち“年間約1兆円の社会的・経済的損失と約1000万の人命(WHO試算)”を救う挑戦であり,そのための「芽生え期」の計画である.また,耐性菌を生まない万能抗菌薬を求める既存の研究から,新たな耐性菌の出現を前提とする着想に切り替え,その次の対策を事前想定したオンリーワンの研究でもある.

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (40 results)

All 2022 2021 2020

All Journal Article (18 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 18 results) Presentation (14 results) (of which Invited: 2 results) Book (8 results)

  • [Journal Article] Triosephosphate isomerase of Streptococcus pneumoniae is released extracellularly by autolysis and binds to host plasminogen to promote its activation.2022

    • Author(s)
      Hirayama S, Domon H, Hiyoshi T, Isono T, Tamura H, Sasagawa K, Takizawa F, Terao Y
    • Journal Title

      FEBS Open Bio

      Volume: 印刷中

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matcha green tea exhibits bactericidal activity against Streptococcus pneumoniae and inhibits functional pneumolysin.2021

    • Author(s)
      Sasagawa K, Domon H, Sakagami R, Hirayama S, Maekawa T, Isono T, Hiyoshi T, Tamura H, Takizawa F, Fukushima Y, Tabeta K, Terao Y
    • Journal Title

      Antibiotics

      Volume: 10(12) Pages: 1550-1550

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clarithromycin inhibits pneumolysin production via downregulation of ply gene transcription despite autolysis activation.2021

    • Author(s)
      Domon H, Isono T, Hiyoshi T, Tamura H, Sasagawa K, Maekawa T, Hirayama S, Yanagihara K, Terao Y
    • Journal Title

      Microbiology Spectrum

      Volume: 9(2)

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of erythromycin on osteoclasts and bone resorption via DEL-1 induction in mice.2021

    • Author(s)
      Tamura H, Maekawa T, Domon H, Hiyoshi T, Hirayama S, Isono T, Sasagawa K, Yonezawa D, Takahashi N, Oda M, Maeda T, Tabeta K, Terao Y
    • Journal Title

      Antibiotics

      Volume: 10 Pages: 312-312

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of neutrophils and neutrophil elastase in pneumococcal pneumonia.2021

    • Author(s)
      Domon H, Terao Y
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: 11 Pages: 615959-615959

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia.2021

    • Author(s)
      Domon H, Maekawa T, Isono T, Furuta K, Kaito C, Terao Y
    • Journal Title

      Sci Rep

      Volume: 11 Pages: 2432-2432

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rice peptide with amino acid substitution inhibits biofilm formation by Porphyromonas gingivalis and Fusobacterium nucleatum.2021

    • Author(s)
      Matsugishi A, Aoki-Nonaka Y, Yokoji-Takeuchi M, Yamada-Hara M, Mikami M, Hayatsu M, Terao Y, Domon H, Taniguchi M, Takahashi N, Yamazaki K, Tabeta K
    • Journal Title

      Arch Oral Biol

      Volume: 121(1) Pages: 104956-104956

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] The proinflammatory cytokine IL-36γ is a global discriminator of harmless microbes and invasive pathogens within epithelial tissues.2020

    • Author(s)
      Macleod T, Ainscough JS, Hesse C, Konzok S, Braun A, Buhl A, Wenzel J, Bowyer P, Terao Y, Herrick S, Wittmann M, Stacey M
    • Journal Title

      Cell Rep

      Volume: 33(11) Pages: 108515-108515

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment of severe pneumonia by hinokitiol in a murine antibiotic-resistant pneumococcal pneumonia model.2020

    • Author(s)
      Isono T, Domon H, Nagai K, Maekawa T, Tamura H, Hiyoshi T, Yanagihara K, Kunitomo E, Takenaka S, Noiri Y, Terao Y
    • Journal Title

      PLOS ONE

      Volume: 15(10) Pages: 240329-240329

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1.2020

    • Author(s)
      Maekawa T, Tamura H, Domon H, Hiyoshi T, Isono T, Yonezawa D, Hayashi N, Takahashi N, Tabeta K, Maeda T, Oda M, Ziogas A, Alexaki VI, Chavakis T, Terao Y, Hajishengallis G
    • Journal Title

      JCI Insight

      Volume: 5(15) Pages: 136706-136706

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sulfated vizantin inhibits biofilm maturation by Streptococcus mutans.2020

    • Author(s)
      Oda M, Kurosawa M, Yamamoto H, Domon H, Takenaka S, Osumi T, Maekawa T, Yamasaki N, Terao Y
    • Journal Title

      Microbiol Immunol

      Volume: 64(7) Pages: 493-501

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Innate immune responses in serum and cerebrospinal fluid from neonates and infants infected with parechovirus-A3 or enteroviruses.2020

    • Author(s)
      Habuka R, Aizawa Y, Izumita R, Domon H, Terao Y, Takihara H, Okuda S, Saitoh A
    • Journal Title

      J Infect Dis

      Volume: 222(4) Pages: 681-689

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of sub-minimum inhibitory concentration of chlorhexidine gluconate on development of in vitro multi-species biofilms. Biofouling.2020

    • Author(s)
      Suzuki Y, Ohsumi T, Isono T, Nagata R, Hasegawa T, Takenaka S, Terao Y, Noiri Y
    • Journal Title

      Biofouling

      Volume: 336(2) Pages: 146-158

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Animal model of periodontitis ― Analysis of experimental ligature-induced periodontitis model in mice ―.2020

    • Author(s)
      Tamura H, Maekawa T, Hiyoshi T, Terao Y:
    • Journal Title

      Methods Mol Biol

      Volume: 2210 Pages: 237-250

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective effect of hinokitiol against periodontal bone loss in ligature induced experimental periodontitis in mice.2020

    • Author(s)
      Hiyoshi T, Domon H, Maekawa T, Yonezawa D, Kunitomo E, Tabeta K, Terao Y
    • Journal Title

      Arch Oral Biol

      Volume: 112(4) Pages: 104679-104679

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of a novel glass ionomer cement containing flour-zinc-silicate fillers on biofilm formation and dentin ion incorporation.2020

    • Author(s)
      Hasegawa T, Takenaka S, Ohsumi T, Ida T, Ohshima H, Terao Y, Traithawit N, Maeda T, Noiri Y
    • Journal Title

      Clin Oral Investig

      Volume: 24(2) Pages: 963-970

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria predominant in the oral cavity and upper airways.2020

    • Author(s)
      Domon H, Hiyoshi T, Maekawa T, Yonezawa D, Tamura H, Kawabata S, Yanagihara K, Kimura O, Kunitomo E, Terao Y
    • Journal Title

      Microbiol Immunol

      Volume: 63 Pages: 213-222

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adjunct use of mouth rinses with a sonic toothbrush accelerates the detachment of a Streptococcus mutans biofilm: an in vitro study.2020

    • Author(s)
      Ohsumi T, Takenaka S, Sakaue Y, Suzuki Y, Nagata R, Hasegawa T, Ohshima H, Terao Y, Noiri Y
    • Journal Title

      BMC Oral Health

      Volume: 20 Pages: 161-161

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 肺炎球菌ニューモリシンの発現に対するマクロライドの作用解析.2022

    • Author(s)
      土門久哲,磯野俊仁,日吉 巧,田村 光,笹川花梨,前川知樹,平山 悟,_原克紀,寺尾 豊
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺炎球菌トリオースリン酸イソメラーゼは宿主プラスミノーゲンに結合し活性化を促進する.2022

    • Author(s)
      平山 悟,土門久哲,日吉 巧,磯野俊仁,田村 光,笹川花梨,滝澤史雄,寺尾 豊
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 身の回りのウイルスや細菌について.2021

    • Author(s)
      寺尾 豊
    • Organizer
      特別支援学校総合学習,茨城県立霞ヶ浦聾学校
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 肺炎球菌に対する抹茶成分の作用解析.2021

    • Author(s)
      笹川花梨,土門久哲,平山 悟,前川知樹, 磯野俊仁,日吉 巧, 田村 光,寺尾 豊
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] エリスロマイシンのDel-1誘導による骨免疫制御作用の解析.2021

    • Author(s)
      田村 光,土門久哲, 日吉 巧,前田健康,多部田康一,寺尾 豊,前川知樹
    • Organizer
      第6回日本骨免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺炎球菌性肺炎モデルマウスにおけるヒノキチオール気管内投与の治療効果.2021

    • Author(s)
      磯野俊仁,土門久哲,前川知樹,田村 光,日吉 巧,柳原克紀,國友栄治,寺尾 豊
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 抹茶を用いた肺炎の予防・治療研究.2021

    • Author(s)
      寺尾 豊,笹川花梨,坂上莉奈,磯野俊仁,土門久哲
    • Organizer
      抹茶と健康研究会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 中球エラスターゼによる歯周病重症化メカニズム解析と新規治療法への応用.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,米澤大輔,多部田 康一,寺尾 豊
    • Organizer
      令和2年度新潟歯学会第2回例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Erythromycin regulates bone metabolism through induction of Del-1.2020

    • Author(s)
      Tamura H, Maekawa T, Domon H, Hiyoshi T, Isono T, Yonezawa D, Maeda T, Terao Y, Tabeta K
    • Organizer
      第63回秋季日本歯周病学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 好中球エラスターゼによる歯周炎重症化メカニズム解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,磯野俊仁,寺尾 豊,多部田康一
    • Organizer
      第63回秋季日本歯周病学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] エリスロマイシンによるDel-1誘導を介した骨代謝の制御.2020

    • Author(s)
      田村 光,前川知樹,土門久哲,日吉 巧,前田健康,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒノキチオールの抗菌活性および抗炎症作用によるマウス歯牙結紮歯周炎モデル骨吸収抑制作用の解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,國友栄治,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 宿主由来エラスターゼはHLAクラスII発現を抑制する.2020

    • Author(s)
      土門久哲,前川知樹,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] マウス歯牙結紮歯周炎モデルにおけるヒノキチオールの骨吸収抑制作用の解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,米澤大輔,國友栄治,寺尾 豊,多部田康一
    • Organizer
      第63回春季歯周病学会学術大会
    • Related Report
      2020 Research-status Report
  • [Book] 微生物学.歯科衛生士書き込み式学習ノート1 専門基礎科目編 人体の構造と機能/歯・口腔の構造と機能/疾病の成り立ち及び回復過程の促進 第2版 改訂第3刷2022

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      302
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] パーフェクトマスター 口腔微生物学・免疫学 改訂第3刷2021

    • Author(s)
      寺尾 豊
    • Total Pages
      93
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] 口腔微生物学・免疫学 第5版2021

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      315
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] 微生物学.歯科衛生士書き込み式学習ノート?@ 専門基礎科目編 人体の構造と機能/歯・口腔の構造と機能/疾病の成り立ち及び回復過程の促進 第2版 改訂第3刷2021

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      302
    • Publisher
      医歯薬出版
    • Related Report
      2020 Research-status Report
  • [Book] 口腔微生物学・免疫学 第4版 改訂第6刷2020

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      303
    • Publisher
      医歯薬出版
    • Related Report
      2020 Research-status Report
  • [Book] パーフェクトマスター 口腔微生物学・免疫学 改訂第2刷2020

    • Author(s)
      寺尾 豊
    • Total Pages
      93
    • Publisher
      医歯薬出版
    • Related Report
      2020 Research-status Report
  • [Book] Aroma Research:ヒノキチオールの肺炎および歯周病に対する効果2020

    • Author(s)
      寺尾 豊
    • Total Pages
      70
    • Publisher
      Fragrance Journal
    • Related Report
      2020 Research-status Report
  • [Book] 和香通信:薬剤耐性(AMR)肺炎球菌による肺炎に対するヒノキチオールの治療効果2020

    • Author(s)
      寺尾 豊
    • Total Pages
      30
    • Publisher
      日本産天然精油連絡協議会
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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