| Project/Area Number |
23K13876
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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 38020:Applied microbiology-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
アザム アアハエルマン 国立感染症研究所, 治療薬・ワクチン開発研究センター, 研究員 (80852780)
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| Project Period (FY) |
2023-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | Phage therapy / Bacteriophage / Antimicrobial resistance / synthetic bacteriophage / phage therapy / Staphylococcal phage / L-form / Long circulating phage |
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| Outline of Research at the Start |
By using synthetic platform that has been recently established, I propose to develop phage with superior antimicrobial efficacy by enhancing their stability through capsid mdification, and improving their bactericidal activity by loading CRISPR-Cas13a or other antimicrobial genes.
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| Outline of Annual Research Achievements |
At the beginning of this research, an assessment was conducted to compare the therapeutic efficacy of bacteriophages against that of antibiotics. The results demonstrated that the optimal therapeutic outcomes were achieved through a combination of bacteriophages and antibiotics, underscoring the significance of carefully selecting the appropriate bacteriophages for use (Azam et al., Microbiology Spectrum, 2024). Subsequently, a synthetic approach was developed and implemented, leading to the successful generation of various synthetic bacteriophages for various purposes including for detection (Tamura et al. Communication Biology. 2024) or phage with enhanced therapeutic activity through this methodology (Azam et al. BioRxive 2024).
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The progress of the research project has been notably positive, with several significant milestones having been achieved. Among these accomplishments, two peer-reviewed publications have been produced. In one of these publications, I have been credited as the first author, demonstrating primary responsibility and substantial involvement in the study. In the other publication, I have been acknowledged as the second author, reflecting a significant, role in the research efforts. These achievements underscore the productive and impactful nature of the ongoing research activities.
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| Strategy for Future Research Activity |
In the current study, we identified that the synthetic method for bacteriophage production is limited to phages with genomes up to 60 kilobases. This limitation necessitates protocol optimization, as many phages with broad host ranges typically possess genomes exceeding 100 kilobases. Additionally, we discovered that many clinically significant bacteria harbor anti-phage defense systems, potentially compromising the efficacy of phage therapy. However, it was also found that certain phages contain anti-defense mechanisms, referred to as anti-defense canceller, which can counteract these bacterial defenses (Azam et al., BioRxiv, 2024). We aim to further evaluate this anti-defense strategy in the ongoing study.
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