2021 Fiscal Year Final Research Report
Mechanism of action analysis of novel antibiotics in host factor contribution to therapeutic efficacy
| Project/Area Number |
19K07140
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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 47050:Environmental and natural pharmaceutical resources-related
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 宿主と微生物の相互作用 / 新規抗生物質 / ライソシンE / アポリポプロテインA-I / lipid II |
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| Outline of Final Research Achievements |
In this study, we succeeded in unraveling the mechanism of action of the host factor apolipoprotein A-I (ApoA-I), which enhances the antimicrobial activity of lysocin E, with a detailed step-by-step description of the mechanism of action. The results suggest that lysocin E utilizes the interaction between host and microbial factors to increase antimicrobial activity, which also contributes to therapeutic efficacy in mice systemic infection model. Since there have been no previous reports of antimicrobials that exhibit higher activity in the host environment, it can be concluded that lysocin E is a new class of antimicrobial agent. Furthermore, we found that the activity of several antimicrobial compounds was enhanced by various host factors, indicating that this phenomenon is not limited to lysocin E.
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| Free Research Field |
化学療法学
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| Academic Significance and Societal Importance of the Research Achievements |
ライソシンEの高い治療効果を発揮する理由を明らかにすることができ、その臨床応用性について確証することができた。さらに宿主と微生物の相互作用を利用する、新しいクラスの抗菌薬の存在を明らかにすることができた。これまで宿主因子は抗菌活性を阻害する方向で考えられてきたため、宿主環境下においてより高い活性を示す抗菌治療薬の存在は想定されていない。従って、これまで注目されていない未知の抗菌化合物群の存在が期待でき、それを示唆するデータが得られてきている。本研究成果をもとに新しい手法の抗菌薬探索法を確立することが可能である。
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