| Project/Area Number |
20K07509
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49050:Bacteriology-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Suzuki Masato 国立感染症研究所, 薬剤耐性研究センター, 主任研究官 (70444073)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 薬剤耐性 / cGAS / 病原性 / Acinetobacter baummannii / 細菌 |
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| Outline of Research at the Start |
cGAS (cyclic GMP-AMP synthase) から合成されるcGAMP (cyclic GMP-AMP) は、原核細胞と真核細胞、即ち分類学上の生物界を超えてクロスキングダムな生物活性を有するセカンドメッセンジャーであることが明らかとなってきた。本研究では、細菌cGASと薬剤耐性・病原性との関連性に焦点を置き、Acinetobacter baumannii流行株にてcGAMP標的因子の網羅的同定と機能解析を行い、細菌cGASを介した生命現象の分子機構を明らかにすることを企図した。
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| Outline of Final Research Achievements |
Under the global concern regarding antimicrobial resistance in gram-negative bacterial pathogens, our objective was to investigate the underlying biological mechanisms regulated by the cyclic GMP-AMP synthase (cGAS) gene, which is encoded on an antimicrobial resistance plasmid found in the epidemic strain of Acinetobacter baumannii clinically isolated in Japan. Using wild-type, cGAS-deficient, and cGAS-complemented strains of A. baumannii, we conducted comparative analyses to evaluate the impact of cGAS on antimicrobial resistance and virulence. Considering the strain-specific preservation of cGAS among strains, it is regarded as a potential factor contributing to variations in phenotypes and regional/ethnic specificities among strains. This study successfully integrated the fields of fundamental bacteriology and molecular epidemiology of clinically significant bacterial species, resulting in novel insights.
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| Academic Significance and Societal Importance of the Research Achievements |
病原細菌において菌株毎に保存性が異なるcGASは、菌株間の表現系の差違や菌株の地域・人種特異性などを説明することが可能な因子と考えられ、本研究から基礎細菌学と感染症起因菌の分子疫学の知見を結び付ける成果を得られた。
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