| Project/Area Number |
20K17475
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54030:Infectious disease medicine-related
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
Kamoshida Go 京都薬科大学, 薬学部, 助教 (40707410)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Acinetobacter baumannii / 実験進化 / 人工呼吸器関連性肺炎 / コリスチン / LPS / アシネトバクター / 線毛 / 代謝変化 / 薬剤耐性 / 細菌-宿主相互作用 / 敗血症 / 肺炎 |
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| Outline of Research at the Start |
本研究では，これまでに申請者が細菌の病原性解析のために構築した細菌-宿主相互作用実験系を利用し，アシネトバクター バウマニ (Acinetobacter bauamnnii) を実験的に進化させ，宿主からのストレスに適応した菌株を樹立することで，細菌固有の病原性を明らかにする．さらに，それら細菌-宿主相互作用を標的とした感染症治療/制御の新規戦略を開発することを目的に研究を行う．
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| Outline of Final Research Achievements |
Recently, formerly harmless or low-pathogenic bacteria have presented problems as they acquire high pathogenicity and develop drug resistance through the process of adaptation to various environmental stresses. Acinetobacter baumannii, characterized by its remarkable adaptability and drug resistance, has emerged as a prominent causative bacterium of nosocomial infections. This study aimed to investigate the inherent pathogenicity of A. baumannii, we focused on the environmental adaptability of this bacteria and establish environmentally adapted strains using in vivo/vitro experimental evolution approaches. By experimentally generating strains exhibiting strong adherence to tracheal intubation tubes of artificial respirators and conducted comprehensive analyses its virulence. We elucidated the changes in essential pili responsible for bacterial adhesion and the crucial alterations in amino acid metabolism for growth and survival in host environment.
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| Academic Significance and Societal Importance of the Research Achievements |
多剤耐性 Acinetobacter baumannii はWHO・CDC・AMED が作成した Priority Pathogen List でも，新規抗菌薬が早急に必要な病原細菌として最も高い優先順位に定められており，早急な感染制御が求められている．A. baumannii は院内施設や医療機器等に定着し，制御困難な薬剤耐性菌が院内で蔓延，易感染性患者に感染した場合は高い致死率を示す．本研究により，医療機器に定着/増殖した菌を感染源とする人工呼吸器関連性肺炎の発症メカニズムと高病原化に寄与する菌の進化に関する新たな知見を提示できた．本成果は，本菌の新規治療/制御法の開発に繋がる．
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