In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans
In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans
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Eucarobustol E 对白色念珠菌的体外抗菌膜活性。
DOI：
10.1128/aac.02707-16
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发表时间：
2017-08-01
影响因子：
4.9
通讯作者：
Kong, Ling-Yi
中科院分区：
文献类型：
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作者：
Liu, Rui-Huan;Shang, Zhi-Chun;Kong, Ling-Yi
甲酰间苯三酚类萜类化合物是一类重要的天然产物，具有多种生物活性。我们的抗真菌药敏试验表明，一个桉树粗壮衍生的FPMs，eucarobuburine E（EE），对白色念珠菌生物膜在16 μ g/ml的浓度产生了强烈的抑制作用。EE被发现可以阻断酵母菌到菌丝的转变，并降低生物膜细胞的细胞表面疏水性。RNA测序和实时逆转录PCR分析表明，暴露于16 μ g/ml EE导致参与菌丝生长的基因（EFG 1，CPH 1，TEC 1，EED 1，UME 6和HGC 1）和细胞表面蛋白基因（ALS 3，HWP 1和SAP 5）的表达水平显着降低。有趣的是，响应EE，参与麦角固醇生物合成的基因下调，而法尼醇编码基因（DPP 3）上调，这些发现与麦角固醇和法尼醇的定量结果一致。结合负调控基因（TUP 1、NRG 1）的明显上调，推测EE抑制碳流向麦角甾醇转化，触发了菌丝生长的负调控机制，最终导致生物膜抑制。
Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta-derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against Candida albicans biofilms at a concentration of 16 mu g/ml. EE was found to block the yeast-to-hypha transition and reduce the cellular surface hydrophobicity of the biofilm cells. RNA sequencing and real-time reverse transcription-PCR analysis showed that exposure to 16 mu g/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface protein genes (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene (DPP3) was upregulated, and these findings were in agreement with those from the quantification of ergosterol and farnesol. Combined with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibition of carbon flow to ergosterol triggered the mechanisms of the negative regulation of hyphal growth and eventually led to biofilm inhibition.