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异缬草醇的抗真菌活性涉及线粒体功能障碍、生物膜形成抑制和对 细胞细胞壁完整性的损伤。

Isoespintanol Antifungal Activity Involves Mitochondrial Dysfunction, Inhibition of Biofilm Formation, and Damage to Cell Wall Integrity in .

机构信息

Biology Department, Faculty of Basic Sciences, Universidad de Córdoba, Montería 230002, Colombia.

Chemistry Department, Faculty of Basic Sciences, Universidad de Córdoba, Montería 230002, Colombia.

出版信息

Int J Mol Sci. 2023 Jun 15;24(12):10187. doi: 10.3390/ijms241210187.

Abstract

The growing increase in infections caused by , associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of fungal biofilms, the mitochondrial membrane potential (ΔΨm), and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.

摘要

由 引起的感染不断增加,加上其耐药性和随之而来的高死亡率,尤其是在免疫功能低下的人群中,如今引发了一个严重的全球公共卫生问题。为了寻找新的潜在药物候选物,这些候选物可用作治疗或控制这些致病酵母菌感染的佐剂,本研究的目的是评估异艾杜醇(ISO)对真菌生物膜形成、线粒体膜电位(ΔΨm)的作用,以及其对细胞壁完整性的影响。我们报告了 ISO 抑制生物膜形成的能力高达 89.35%,在所有情况下都高于两性霉素 B(AFB)的表达值。使用罗丹明 123(Rh123)进行的流式细胞术实验表明,ISO 能够导致这些细胞中线粒体功能障碍。同样,使用钙荧光白(CFW)并通过流式细胞术分析表明,ISO 通过刺激几丁质合成来影响细胞壁的完整性;通过透射电子显微镜(TEM)也观察到了细胞壁完整性的这些变化。这些机制参与了这种单萜的抗真菌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/373e/10299589/6bf5b65124f0/ijms-24-10187-g001.jpg

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