| Project/Area Number |
21K15431
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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 49050:Bacteriology-related
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
Chen Xinyue 東京工業大学, 生命理工学院, 助教 (50817369)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Candida species / NADPH oxidase / fungal ROS production / ROS production / NOX genes / Drug resistance / Pathogenic Candida / hepatic cell / reactive oxygen species |
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| Outline of Research at the Start |
Candida species can invade human body and reach liver to cause systemic fungal infection. Thus, understanding the interaction between Candida virulence factor and host response is important. This study aims to investigate the induction mechanism of hepatocyte death by fungal reactive oxygen species.
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| Outline of Final Research Achievements |
This study investigated how two NADPH oxidase genes from Candida species contribute to the interplay between fungi and hepatocytes and involve in oxidative stress responses. Our results demonstrated CgNOX1 in Candida glabrata plays important roles in fungal ROS production, the response to oxidative stress and ferric reductase activity as well as affects the production of inflammatory cytokines in hepatocytes following C. glabrata infection. In Candida albicans, CaCFL11 showed enhanced expression under the co-culture with hepatocytes, resulting in ROS production. By using a GFP reporter system, the regulation of CaCFL11 promoters was studied during co-incubation with hepatocytes and under oxidative stress. Our results suggested CaCFL11 upstream region from -200 bp to the start codon was essential for transcriptional regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、カンジダ属菌に由来する活性酸素ROS産生酵素NADPHオキシダーゼ遺伝子の機能および肝細胞との共培養時の遺伝子発現誘導を理解するための基礎研究である。真菌ROS産生を介して肝細胞の細胞死を誘導する分子メカニズムを理解することで、肝臓さらに全身性カンジダ症に対する臨床治療法の確立につながると考えている。真菌ROS産生を抑制することができれば、肝細胞の細胞死を防ぐことができ、カンジダ属菌が腸管から肝臓、さらには全身への侵襲を食い止めることができるのではないかと期待される。
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