| 研究課題/領域番号 |
20K08832
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分54030:感染症内科学関連
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
アブケセーサ イマド 国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (10749906)
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| 研究期間 (年度) |
2020-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2022年度: 2,990千円 (直接経費: 2,300千円、間接経費: 690千円)
2021年度: 780千円 (直接経費: 600千円、間接経費: 180千円)
2020年度: 520千円 (直接経費: 400千円、間接経費: 120千円)
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| キーワード | Mycology / Eumycetoma / Galleria mellonella / Antifungal / Madurella mycetomatis / Transcriptomics / Mycetoma / RNA-Seq / Tropical disease |
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| 研究開始時の研究の概要 |
The purpose, scientific significance, and originality of the research project
1- Determine the efficacy of different antifungal agents (fosravuconazole and itraconazole) in an in vivo Madurella mycetomatis grain model in Galleria mellonella larvae 2- Characterize the biological pathways leading to eradication of the pathogen by the drug in pathogen and host 3- Identify molecular markers associated with the response towards the studied antifungal agents
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| 研究実績の概要 |
In vivo transcriptomics analysis was completed. To determine how a pathogen within a host is responding to treatment, we needed to know first how the pathogen responds to the antifungal agent outside the host (in vitro). We designed an in vitro study to determine how Madurella mycetomatis (Mm) became more tolerant to antifungal agents. We cultured isolate from mycetoma patients in the presence of antifungal agents. We exposed Mm to sub-inhibitory concentrations of itraconazole, terbinafine, ravuconazole, Ampotheracin B, Posaconazole and Olorofim and determine the transcriptomic response towards these drugs. We generated RNA-seq libraries 5 replicates per 3 time points (n=105, including Mm treated with 1%DMSO). The analysis of the in vitro data was completed.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
All planned tasks during 2023 was completed.
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| 今後の研究の推進方策 |
During 2024 our aim was to integrate transcriptomics data from in vivo and in vitro systems. This data then helps us to understand what the main transcriptomic response of the pathogen is to the antifungal agent. In the in vivo situation the response to the antifungal agent is combined with the response of the pathogen to the host. That is a more complicated system. Therefore, combining the in vitro and in vivo response towards the antifungal agents makes it easier to decipher which response is associated with what in this model system. Finally, we are planning to draft a manuscript for submission.
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