Small-molecule suppressors of Candida albicans biofilm formation synergistically enhance the antifungal activity of amphotericin B against clinical Candida isolates.
Small-molecule suppressors of Candida albicans biofilm formation synergistically enhance the antifungal activity of amphotericin B against clinical Candida isolates.
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DOI：
10.1021/cb400009f
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发表时间：
2013-04-19
影响因子：
4
通讯作者：
Cichewicz, Robert H.
中科院分区：
文献类型：
--
作者：
You, Jianlan;Du, Lin;King, Jarrod B.;Hall, Brian E.;Cichewicz, Robert H.
A new class of fungal biofilm inhibitors represented by shearinines D (3) and E (4) were obtained from a Penicillium sp. isolate. The inhibitory activities of 3 and 4 were characterized using a new imaging flow-cytometer technique, which enabled the rapid phenotypic analysis of Candida albicans cell types (budding yeast cells, germ tube cells, pseudohyphae, and hyphae) in biofilms populations. The results were confirmed by experimental data obtained from three-dimensional confocal laser scanning microscopy and 2,3- bis-(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays. These data indicate that 3 and 4 inhibited C. albicans biofilm formation by blocking the outgrowth of hyphae at a relatively late stage of biofilm development (IC50 = 8.5 μM and 7.6 μM, respectively). However, 3 and 4 demonstrated comparatively weak activity at disrupting existing biofilms. Compounds 3 and 4 also exhibited synergistic activities with amphotericin B against C. albicans and others clinical Candida isolates by enhancing the potency of amphotericin B up to eight-fold against cells in both developing and established biofilms. These data suggest that the Candida biofilm disruption and amphotericin B potentiating effects of 3 and 4 could be mediated through multiple biological targets. The shearinines are good tools for testing the potential advantages of using adjunctive therapies in combination with antifungals.
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DOI：
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发表时间：
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期刊：
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影响因子：
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Cichewicz, Robert H.
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DOI：
10.1086/651200
发表时间：
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期刊：
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影响因子：
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