Quinone derivatives isolated from the endolichenic fungus Phialocephala fortinii are Mdr1 modulators that combat azole resistance in Candida albicans.
Quinone derivatives isolated from the endolichenic fungus Phialocephala fortinii are Mdr1 modulators that combat azole resistance in Candida albicans.
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从内生真菌 Phialocephala fortinii 中分离出的醌衍生物是 Mdr1 调节剂，可对抗白色念珠菌中的唑类耐药性
DOI：
10.1038/srep33687
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发表时间：
2016-09-21
影响因子：
4.6
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Xie F;Chang W;Zhang M;Li Y;Li W;Shi H;Zheng S;Lou H
念珠菌病原体中主要的唑耐药机制之一是药物外排泵的上调，这损害了唑的疗效并导致治疗失败。唑类抗真菌药物与外排泵抑制剂的结合是对抗真菌感染的一种有前途的策略。高通量筛选从内生真菌培养中获得的150个提取物，发现phalocephala fortini提取物具有逆转唑抗性的有效活性。从该菌株中共分离得到15个醌类化合物，包括11个新化合物和4个已知化合物。在这些化合物中，palmarumycin P3(3)和phalocephalarin B(8)特异性调节MDR1的表达，抑制药物外排泵的活性，从而逆转唑耐药性。本研究揭示了Mdr1靶向是发现抗真菌药物耐药新药物的另一种机制。
One of the main azole-resistance mechanisms in Candida pathogens is the upregulation of drug efflux pumps, which compromises the efficacy of azoles and results in treatment failure. The combination of azole-antifungal agents with efflux pump inhibitors represents a promising strategy to combat fungal infection. High-throughput screening of 150 extracts obtained from endolichenic fungal cultures led to the discovery that the extract of Phialocephala fortinii exhibits potent activity for the reversal of azole resistance. From P. fortinii cultures, a total of 15 quinone derivatives, comprising 11 new derivatives and 4 known compounds, were obtained. Among these compounds, palmarumycin P3 (3) and phialocephalarin B (8) specifically modulate the expression of MDR1 to inhibit the activity of drug efflux pumps and therefore reverse azole resistance. The present study revealed Mdr1 targeting as an alternative mechanism for the discovery of new agents to fight antifungal drug resistance.
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