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甘草素诱导白念珠菌中两个主要凋亡基因 MCA1 和 NUC1 的过度表达。

Glabridin induces overexpression of two major apoptotic genes, MCA1 and NUC1, in Candida albicans.

机构信息

Department of Medical Laboratory Sciences, Sari Branch, Islamic Azad University, Sari, Iran.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

J Glob Antimicrob Resist. 2017 Dec;11:52-56. doi: 10.1016/j.jgar.2017.08.006. Epub 2017 Aug 24.

DOI:10.1016/j.jgar.2017.08.006
PMID:28844974
Abstract

OBJECTIVES

The growing trend in emergence of antifungal-resistant Candida strains has recently inspired researchers to design new antifungal agents with novel mechanisms of action. Glabridin is a natural substrate with multiple biological activities. In this study, the antifungal effects and possible mechanism of action of glabridin were investigated.

METHODS

Minimum inhibitory concentrations (MICs) of glabridin against fluconazole (FLU)-resistant and FLU-susceptible Candida albicans strains were investigated according to Clinical and Laboratory Standards Institute (CLSI) guidelines. To investigate the possible mechanism of action, expression of two critical genes involved in yeast apoptosis (MCA1 and NUC1) was assayed by real-time PCR.

RESULTS

FLU-susceptible and FLU-resistant C. albicans strains showed the same glabridin MICs (MIC, 8μg/mL). Therefore, a distinct azole-independent mechanism might be responsible for the inhibitory activity of glabridin. Overexpression of MCA1 and NUC1 was observed in C. albicans cells treated with glabridin, suggesting the involvement of apoptosis signalling in C. albicans strains exposed to glabridin.

CONCLUSION

This study suggests that glabridin might be considered a safe agent to fight against C. albicans strains.

摘要

目的

最近,抗真菌药物耐药性念珠菌菌株的出现呈增长趋势,这促使研究人员设计具有新型作用机制的新型抗真菌药物。甘草素是一种具有多种生物学活性的天然底物。本研究旨在探讨甘草素的抗真菌作用及其可能的作用机制。

方法

根据临床和实验室标准协会(CLSI)指南,测定了甘草素对氟康唑(FLU)耐药和 FLU 敏感的白色念珠菌菌株的最低抑菌浓度(MIC)。为了研究可能的作用机制,通过实时 PCR 检测了参与酵母细胞凋亡的两个关键基因(MCA1 和 NUC1)的表达。

结果

FLU 敏感和 FLU 耐药的白色念珠菌菌株显示出相同的甘草素 MIC(MIC,8μg/mL)。因此,甘草素的抑制活性可能是通过一种独特的唑类药物非依赖性机制实现的。在甘草素处理的白色念珠菌细胞中观察到 MCA1 和 NUC1 的过表达,表明凋亡信号参与了暴露于甘草素的白色念珠菌菌株。

结论

本研究表明,甘草素可能被认为是一种对抗白色念珠菌菌株的安全药物。

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