Liu Rui-Huan, Shang Zhi-Chun, Li Tian-Xiao, Yang Ming-Hua, Kong Ling-Yi
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.02707-16. Print 2017 Aug.
Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the -derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against biofilms at a concentration of 16 μg/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 μg/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (, , , , , and ) and cell surface protein genes (, , and ). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene () 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 (, ), 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.
甲酰基间苯三酚聚酮类化合物(FPMs)是具有多种生物活性的重要天然产物类型。我们的抗真菌药敏试验表明,一种源自[具体来源未提及]的FPMs,即eucarobustol E(EE),在浓度为16μg/ml时对[具体真菌名称未提及]生物膜具有强烈的抑制作用。发现EE可阻断酵母向菌丝的转变,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16μg/ml的EE会导致参与菌丝生长的基因([具体基因名称未提及])和细胞表面蛋白基因([具体基因名称未提及])的表达水平显著降低。有趣的是,响应EE时,参与麦角固醇生物合成的基因被下调,而法尼醇编码基因([具体基因名称未提及])被上调,这些发现与麦角固醇和法尼醇定量结果一致。结合负调控基因([具体基因名称未提及])的明显升高,我们推测EE对流向麦角固醇的碳流的抑制触发了菌丝生长负调控机制,并最终导致生物膜抑制。