{"title":"Bamemacrolactine C 对马拉尼菲氏菌的抗真菌活性及其可能的作用机制。","authors":"Cuiping Jiang, Guangfu Feng, Zhou Wang, Kai Liu, Xinjian Qu, Yonghong Liu, Xiangxi Yi, Chenghai Gao","doi":"10.1093/jambio/lxae297","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>The present study aims to investigate the in vitro antifungal activity and mechanism of action of bamemacrolactine C (BAC), a new 24-membered macrolide compound, against Talaromyces marneffei.</p><p><strong>Methods and results: </strong>The test drug BAC initially demonstrated antifungal activity through a paper disk diffusion assay, followed by determination of the minimum inhibitory concentration value of 35.29 μg ml-1 using microdilution. The association study revealed that combination therapy exhibited additive effects (0.5 < FICI < 1.0) when combined BAC with either amphotericin B or fluconazole. A time-growth assay confirmed that treatment with 35.29 μg ml-1 of BAC completely inhibited the growth of T. marneffei and exhibited antifungal effects. Micromorphological analysis using scanning electron microscopy and transmission electron microscopy photomicrographs revealed that BAC treatment induced morphological damage in fungal cells compared to the control group. Transmembrane protein assays showed a significant reduction in the levels of Na+/K+-ATPase (P < .05) and Ca2+-ATPase (P < .01) compared to the control group. Intracellular enzyme assays demonstrated that BAC treatment significantly decreased ATP, malate dehydrogenase, and succinate dehydrogenase content (P < .01). The combination of proteomics and parallel reaction monitoring (PRM) verification indicated that BAC exhibits an antifungal mechanism against T. marneffei by downregulating ATP citric acid lyase (ACLY) levels , potentially affecting the tricarboxylic acid (TCA) cycle. Besides, the binding model of BAC and the ACLY also shows a good docking score.</p><p><strong>Conclusions: </strong>The findings suggest that BAC exhibits antifungal activity against T. marneffei, elucidating its multifaceted mechanism of action involving disruption of cell membranes' integrity and inhibition of intracellular enzyme activities, in which the modulation of ACLY in the TCA cycle may play an important role.</p>","PeriodicalId":15036,"journal":{"name":"Journal of Applied Microbiology","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antifungal activity of bamemacrolactine C against Talaromyces marneffei and its possible mechanisms of action.\",\"authors\":\"Cuiping Jiang, Guangfu Feng, Zhou Wang, Kai Liu, Xinjian Qu, Yonghong Liu, Xiangxi Yi, Chenghai Gao\",\"doi\":\"10.1093/jambio/lxae297\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>The present study aims to investigate the in vitro antifungal activity and mechanism of action of bamemacrolactine C (BAC), a new 24-membered macrolide compound, against Talaromyces marneffei.</p><p><strong>Methods and results: </strong>The test drug BAC initially demonstrated antifungal activity through a paper disk diffusion assay, followed by determination of the minimum inhibitory concentration value of 35.29 μg ml-1 using microdilution. The association study revealed that combination therapy exhibited additive effects (0.5 < FICI < 1.0) when combined BAC with either amphotericin B or fluconazole. A time-growth assay confirmed that treatment with 35.29 μg ml-1 of BAC completely inhibited the growth of T. marneffei and exhibited antifungal effects. Micromorphological analysis using scanning electron microscopy and transmission electron microscopy photomicrographs revealed that BAC treatment induced morphological damage in fungal cells compared to the control group. Transmembrane protein assays showed a significant reduction in the levels of Na+/K+-ATPase (P < .05) and Ca2+-ATPase (P < .01) compared to the control group. Intracellular enzyme assays demonstrated that BAC treatment significantly decreased ATP, malate dehydrogenase, and succinate dehydrogenase content (P < .01). The combination of proteomics and parallel reaction monitoring (PRM) verification indicated that BAC exhibits an antifungal mechanism against T. marneffei by downregulating ATP citric acid lyase (ACLY) levels , potentially affecting the tricarboxylic acid (TCA) cycle. Besides, the binding model of BAC and the ACLY also shows a good docking score.</p><p><strong>Conclusions: </strong>The findings suggest that BAC exhibits antifungal activity against T. marneffei, elucidating its multifaceted mechanism of action involving disruption of cell membranes' integrity and inhibition of intracellular enzyme activities, in which the modulation of ACLY in the TCA cycle may play an important role.</p>\",\"PeriodicalId\":15036,\"journal\":{\"name\":\"Journal of Applied Microbiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-12-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/jambio/lxae297\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/jambio/lxae297","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：研究新型24元大环内酯类化合物Bamemacrolactine C （BAC）对马尔尼菲Talaromyces marneffei的体外抑菌活性及其作用机制。方法与结果：试验药物BAC通过纸片扩散法初步显示抗真菌活性，微量稀释法测定其最低抑菌浓度（MIC）值为35.29 μg·mL-1。结论：BAC对T. marneffei具有一定的抗真菌活性，揭示了其破坏细胞膜完整性、抑制胞内酶活性等多方面的作用机制，其中TCA循环中ACLY的调节可能发挥了重要作用。
Antifungal activity of bamemacrolactine C against Talaromyces marneffei and its possible mechanisms of action.
Aims: The present study aims to investigate the in vitro antifungal activity and mechanism of action of bamemacrolactine C (BAC), a new 24-membered macrolide compound, against Talaromyces marneffei.
Methods and results: The test drug BAC initially demonstrated antifungal activity through a paper disk diffusion assay, followed by determination of the minimum inhibitory concentration value of 35.29 μg ml-1 using microdilution. The association study revealed that combination therapy exhibited additive effects (0.5 < FICI < 1.0) when combined BAC with either amphotericin B or fluconazole. A time-growth assay confirmed that treatment with 35.29 μg ml-1 of BAC completely inhibited the growth of T. marneffei and exhibited antifungal effects. Micromorphological analysis using scanning electron microscopy and transmission electron microscopy photomicrographs revealed that BAC treatment induced morphological damage in fungal cells compared to the control group. Transmembrane protein assays showed a significant reduction in the levels of Na+/K+-ATPase (P < .05) and Ca2+-ATPase (P < .01) compared to the control group. Intracellular enzyme assays demonstrated that BAC treatment significantly decreased ATP, malate dehydrogenase, and succinate dehydrogenase content (P < .01). The combination of proteomics and parallel reaction monitoring (PRM) verification indicated that BAC exhibits an antifungal mechanism against T. marneffei by downregulating ATP citric acid lyase (ACLY) levels , potentially affecting the tricarboxylic acid (TCA) cycle. Besides, the binding model of BAC and the ACLY also shows a good docking score.
Conclusions: The findings suggest that BAC exhibits antifungal activity against T. marneffei, elucidating its multifaceted mechanism of action involving disruption of cell membranes' integrity and inhibition of intracellular enzyme activities, in which the modulation of ACLY in the TCA cycle may play an important role.
期刊介绍：
Journal of & Letters in Applied Microbiology are two of the flagship research journals of the Society for Applied Microbiology (SfAM). For more than 75 years they have been publishing top quality research and reviews in the broad field of applied microbiology. The journals are provided to all SfAM members as well as having a global online readership totalling more than 500,000 downloads per year in more than 200 countries. Submitting authors can expect fast decision and publication times, averaging 33 days to first decision and 34 days from acceptance to online publication. There are no page charges.
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