Polyketide Glycosides from Bionectria ochroleuca Inhibit Candida albicans Biofilm Formation

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• 作者：Bin Wang ; Jianlan You ; Jarrod B. King ; Shengxin Cai ; Elizabeth Park ; Douglas R. Powell ; Robert H. Cichewicz
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：October 24, 2014
• 年：2014
• 卷：77
• 期：10
• 页码：2273-2279
• 全文大小：320K
• ISSN：1520-6025

文摘

One of the challenges presented by Candida infections is that many of the isolates encountered in the clinic produce biofilms, which can decrease these pathogens鈥?susceptibilities to standard-of-care antibiotic therapies. Inhibitors of fungal biofilm formation offer a potential solution to counteracting some of the problems associated with Candida infections. A screening campaign utilizing samples from our fungal extract library revealed that a Bionectria ochroleuca isolate cultured on Cheerios breakfast cereal produced metabolites that blocked the in vitro formation of Candida albicans biofilms. A scale-up culture of the fungus was undertaken using mycobags (also known as mushroom bags or spawn bags), which afforded four known [TMC-151s C鈥揊 (1鈥?b>4)] and three new [bionectriols B鈥揇 (5鈥?b>7)] polyketide glycosides. All seven metabolites exhibited potent biofilm inhibition against C. albicans SC5314, as well as exerted synergistic antifungal activities in combination with amphotericin B. In this report, we describe the structure determination of the new metabolites, as well as compare the secondary metabolome profiles of fungi grown in flasks and mycobags. These studies demonstrate that mycobags offer a useful alternative to flask-based cultures for the preparative production of fungal secondary metabolites.