Suppression of Fluconazole Resistant Candida albicans Biofilm Formation and Filamentation by Methylindole Derivatives.
Suppression of Fluconazole Resistant Candida albicans Biofilm Formation and Filamentation by Methylindole Derivatives.
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DOI：
10.3389/fmicb.2018.02641
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发表时间：
2018
影响因子：
5.2
通讯作者：
Lee J
中科院分区：
文献类型：
--
作者：
Lee JH;Kim YG;Gupta VK;Manoharan RK;Lee J
白色念珠菌是一种机会性真菌病原体，也是临床暴发中最常见的物种。它会引起一系列感染，包括从轻度粘膜感染到严重危及生命的念珠菌血症和播散性念珠菌病。多种毒力因素解释了白色念珠菌的致病性质，其从芽殖酵母到菌丝形式的形态转变以及随后的生物膜形成被认为是念珠菌感染严重性的最重要原因。为了满足新型抗真菌药物的迫切需求，我们使用结晶紫测定法研究了各种甲基吲哚对白色念珠菌的抗生物膜活性，并使用 2,3-双 (2-甲氧基-4-硝基-5-磺基-苯基)-2H-四唑鎓-5-甲酰苯胺还原测定法评估代谢活性。分别通过共焦激光扫描显微镜和扫描电子显微镜测定生物膜形态和厚度的变化。在测试的 21 种甲基吲哚中，0.1 mM (17.5 μg ml-1) 的 1-甲基吲哚-2-羧酸 (1MI2CA) 和 0.1 mM 的 5-甲基吲哚-2-羧酸 (5MI2CA) 可有效抑制白色念珠菌 DAY185 和 ATCC10231 菌株的生物膜形成。此外，1MI2CA和5MI2CA均能有效抑制菌丝形成，从而提高白色念珠菌感染线虫的存活率，且不会引起急性毒性作用。此外，我们的计算机分子模型研究结果与体外观察结果一致。这项研究为制定针对念珠菌病和生物膜相关感染的新策略提供了有用的信息。
Candida albicans is an opportunistic fungal pathogen and most prevalent species among clinical outbreaks. It causes a range of infections, including from mild mucosal infections to serious life-threatening candidemia and disseminated candidiasis. Multiple virulence factors account for the pathogenic nature of C. albicans, and its morphological transition from budding yeast to hyphal form and subsequent biofilm formation is regarded as the most important reason for the severity of Candida infections. To address the demanding need for novel antifungals, we investigated the anti-biofilm activities of various methylindoles against C. albicans using a crystal violet assay, and the metabolic activity was assessed by using a 2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide reduction assay. Changes in biofilm morphologies and thicknesses were determined by confocal laser scanning microscopy and scanning electron microscopy, respectively. Of the 21 methylindoles tested, 1-methylindole-2-carboxylic acid (1MI2CA) at 0.1 mM (17.5 μg ml-1) and 5-methylindole-2-carboxylic acid (5MI2CA) at 0.1 mM effectively inhibited biofilm formation by C. albicans DAY185 and ATCC10231 strains. Moreover, 1MI2CA and 5MI2CA both effectively inhibited hyphal formation, and thus, improved C. albicans infected nematode survival without inducing acute toxic effects. Furthermore, our in silico molecular modeling findings were in-line with in vitro observations. This study provides information useful for the development of novel strategies targeting candidiasis and biofilm-related infections.
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影响因子：
5.7
作者：
Lee J;Attila C;Cirillo SL;Cirillo JD;Wood TK
通讯作者：
Wood TK
影响因子：
5
作者：
Lee, Jin-Hyung;Cho, Hyun Seob;Lee, Jintae
通讯作者：
Lee, Jintae
影响因子：
2.6
作者：
Janeczko, Monika;Maslyk, Maciej;Golczyk, Hieronim
通讯作者：
Golczyk, Hieronim
影响因子：
5.7
作者：
Manoharan RK;Lee JH;Kim YG;Lee J
通讯作者：
Lee J
影响因子：
2.5
作者：
Mathe, Lotte;Van Dijck, Patrick
通讯作者：
Van Dijck, Patrick