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响应小檗碱,白念珠菌抗氧化防御系统的调节。

Modulation of antioxidant defence system in response to berberine in Candida albicans.

机构信息

Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.

Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.

出版信息

Yeast. 2021 Feb;38(2):157-169. doi: 10.1002/yea.3531. Epub 2020 Dec 10.

Abstract

Emergence of multidrug resistant species of Candida is evolving, which advocates an urgent need for the development of new therapeutic strategies and antifungal drugs. Activation of antioxidant defence system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defence genes in the susceptibility to fluconazole in C. albicans and also determined the effect of berberine on growth, antioxidant enzymes and the expression of their genes in C. albicans isolates. Expression of major antioxidant genes was significantly increased in fluconazole-resistant isolates in comparison with the susceptible group. Antifungal susceptibility against berberine showed MIC values ranging from 125 to 500 μg/ml. Berberine treatment caused upregulation of mRNA expression and enzymatic activities of the targeted major antioxidants. Interestingly, C. albicans exhibited efficient antioxidant response at lower concentrations but could not sufficiently alleviate berberine-induced oxidative stress occurring at concentrations greater than 250 μg/ml. Therefore, berberine could serve as a potent Reactive Oxygen Species (ROS)-inducing agent, disrupting the antioxidant system especially in fluconazole-resistant C. albicans to overcome antifungal drug resistance. TAKE AWAYS: Evaluated the role of antioxidant enzymes in FLC resistance in C. albicans Studied the effect of berberine on growth of different C. albicans isolates Investigated the modulation of antioxidant enzymes by berberine in C. albicans Studied the effect of berberine on antioxidant gene expression in C. albicans.

摘要

抗药性念珠菌物种的出现正在演变,这迫切需要开发新的治疗策略和抗真菌药物。白念珠菌抗氧化防御系统的激活被认为是逃避药物毒性的前沿机制。本研究评估了抗氧化防御基因在白念珠菌对氟康唑敏感性中的作用,并确定了小檗碱对念珠菌分离株生长、抗氧化酶及其基因表达的影响。与敏感组相比,氟康唑耐药株中主要抗氧化基因的表达显著增加。对小檗碱的抗真菌药敏试验显示 MIC 值范围为 125 至 500 μg/ml。小檗碱处理导致靶向主要抗氧化剂的 mRNA 表达和酶活性上调。有趣的是,白念珠菌在较低浓度下表现出有效的抗氧化反应,但在浓度大于 250 μg/ml 时,不能充分缓解小檗碱诱导的氧化应激。因此,小檗碱可以作为一种有效的活性氧 (ROS) 诱导剂,破坏抗氧化系统,特别是在氟康唑耐药的白念珠菌中,以克服抗真菌药物耐药性。

要点

评估抗氧化酶在白念珠菌 FLC 耐药中的作用研究小檗碱对不同白念珠菌分离株生长的影响研究小檗碱对白念珠菌抗氧化酶的调节作用研究小檗碱对白念珠菌抗氧化基因表达的影响。

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