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F1Fo ATP合酶作为抗真菌药物靶点的研究进展
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Abstract:
近年来，随着肿瘤化疗、免疫抑制剂及广谱抗菌药物的广泛使用，侵袭性真菌感染的发病率和死亡率在全球呈明显上升趋势，真菌感染已成为严重威胁公共卫生健康的病原体之一。2022年世界卫生组织(WHO)公布的真菌重点病原体清单，也进一步强调了真菌对人类的危害已经达到了危机点，必须引起全球范围内的高度重视。目前临床抗真菌药物种类有限、随之耐药性的产生，因此，寻找新的抗真菌药物靶点尤为重要。F1Fo ATP合酶，作为药物理想分子靶标，一直以来都是研究的热点。随着F1Fo ATP合酶亚基作用机制明了，表明F1Fo ATP合酶作为抗真菌药物靶点的巨大潜力。在此，我们收集整理近年来关于F1Fo ATP合酶的研究成果，从ATP合酶的各亚基展开，进而阐述各亚基的结构功能以及机制，综述各亚基作为靶点的潜在可能性，为抗真菌药物靶点的研究提供参考。
In recent years, with the widespread use of tumor chemotherapy, immunosuppressants and broad-spectrum antimicrobial drugs, the morbidity and mortality of invasive fungal infections have shown a significant upward trend globally, and fungal infections have become one of the pathogens that pose a serious threat to public health. The list of fungal priority pathogens published by the World Health Organization (WHO) in 2022 has also further emphasized the fact that the danger of fungi to human beings has reached a crisis point and must be given high priority globally. The limited availability of clinical antifungal drugs and the consequent emergence of drug resistance have made the search for new antifungal drug targets particularly important, and F1Fo ATP synthase, as an ideal molecular target for drug discovery, has long been a hot research topic. With the clarification of the mechanism of action of the F1Fo ATP synthase subunit, it has been shown that F1Fo ATP synthase has great potential as an antifungal drug target. Here, we collect and organize the research results on F1Fo ATP synthase in recent years, start from the subunits of ATP synthase, and then elaborate the structure, function, and mechanism of each subunit, and review the potential of each subunit as a target, so as to provide a reference for the research of antifungal drug targets.
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