Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor.
Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches to the mechanism of action and influence on Candida albicans virulence factor.
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DOI：
10.1371/journal.pone.0072203
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Valentão P
中科院分区：
文献类型：
--
作者：
Lopes G;Pinto E;Andrade PB;Valentão P
在过去的几十年里，真菌感染，特别是医院感染，在世界各地都有所增加。这种增加刺激了对新抗真菌剂的寻找，特别是那些源自自然的抗真菌剂。在天然产品中，来自海洋的产品在过去几年中越来越受到重视。筛选了三种棕色海藻（Cystoseira nodicaulis (Withering) M. Roberts、Cystoseira usneoides (Linnaeus) M. Roberts 和 Fucusspiralis Linnaeus）的纯化草单宁提取物对人类致病酵母和丝状真菌的抗真菌活性。从所研究的海藻中纯化的根皮单宁提取物分别对酵母和皮肤癣菌具有抑制真菌和杀真菌活性，表明它们作为抗皮肤癣菌剂的兴趣。酵母菌中最易感的是白色念珠菌ATCC 10231，而皮肤癣菌中最易感的是絮状表皮癣菌和红色毛癣菌。由于抗真菌机制构成了限制对市售药物产生耐药性的重要策略，因此研究了纯化的根皮单宁提取物的作用机制。 C. nodicaulis 和 C. usneoides 似乎分别通过影响酵母和皮肤癣菌细胞膜的麦角甾醇组成来发挥作用。螺旋镰刀菌通过降低几丁质的水平来影响皮肤癣菌细胞壁的组成。根皮单宁似乎也会影响呼吸链功能，因为所有研究的物种都显着增加了线粒体脱氢酶的活性，并增加了酵母细胞对罗丹明 123 的掺入。来自螺旋菌的根皮单宁抑制白色念珠菌的二态性转变，导致假菌丝的形成，其粘附上皮细胞的能力减弱。这一发现与白色念珠菌毒力和侵入宿主细胞能力的降低有关，并且对于联合抗真菌治疗（即控制侵袭性念珠菌病）可能具有潜在意义。
In the last few decades, fungal infections, particularly nosocomial, increased all around the world. This increment stimulated the search for new antifungal agents, especially those derived from nature. Among natural products, those from marine sources have gained prominence in the last years. Purified phlorotannins extracts from three brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus) were screened for their antifungal activity against human pathogenic yeast and filamentous fungi. The purified phlorotannins extracts from the studied seaweeds displayed fungistatic and fungicidal activity against yeast and dermatophytes, respectively, pointing to their interest as anti-dermatophyte agent. C. albicans ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum and Trichophyton rubrum were the most susceptible among dermatophytes. Since the antifungal mechanism constitutes an important strategy for limiting the emergence of resistance to the commercially available agents, the mechanism of action of purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides seem to act by affecting the ergosterol composition of the cell membrane of yeast and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall composition by reducing the levels of chitin. Phlorotannins also seem to affect the respiratory chain function, as all of the studied species significantly increased the activity of mitochondrial dehydrogenases and increased the incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis inhibited the dimorphic transition of Candida albicans, leading to the formation of pseudohyphae with diminished capacity to adhere to epithelial cells. This finding is associated with a decrease of C. albicans virulence and capacity to invade host cells and can be potentially interesting for combined antifungal therapy, namely for the control of invasive candidiasis.
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影响因子：
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Lopes G;Sousa C;Silva LR;Pinto E;Andrade PB;Bernardo J;Mouga T;Valentão P
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