Polyketide glycosides from Bionectria ochroleuca inhibit Candida albicans biofilm formation.

Polyketide glycosides from Bionectria ochroleuca inhibit Candida albicans biofilm formation.
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DOI:
10.1021/np500531j
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发表时间:
2014-10-24
影响因子:
5.1
通讯作者:
Cichewicz, Robert H.
Cichewicz, Robert H.
中科院分区:
生物学2区
文献类型:
--
作者:
Wang, Bin;You, Jianlan;King, Jarrod B.;Cai, Shengxin;Park, Elizabeth;Powell, Douglas R.;Cichewicz, Robert H.

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念珠菌感染带来的挑战之一是临床上遇到的许多分离株产生生物膜,这可能会降低这些病原体对标准护理抗生素治疗的敏感性。真菌生物膜形成的抑制剂提供了一种潜在的解决方案,以抵消与念珠菌感染相关的一些问题。利用来自我们的真菌提取物库的样品的筛选活动显示,在Cheerios早餐谷物上培养的Bionectria ochroleuca分离株产生阻断白色念珠菌生物膜体外形成的代谢物。使用真菌袋(也称为蘑菇袋或卵袋)进行真菌的放大培养,其提供了四种已知的[TMC-151 C-F(1-4)]和三种新的[生物胞三醇B-D(5-7)]聚酮糖苷。所有7种代谢产物均表现出对C.白念珠菌SC 5314,以及与阿替霉素B联合发挥协同抗真菌活性。在这份报告中,我们描述了新的代谢产物的结构测定,以及比较培养瓶和菌袋中生长的真菌的次级代谢物谱。这些研究表明,霉菌袋提供了一个有用的替代烧瓶为基础的培养真菌次生代谢产物的制备生产。
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’ 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–F (1–4)] and three new [bionectriols B–D (5–7)] 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.
白色念珠菌在阴道粘膜上形成生物膜。
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