Multidrug resistance is a highly conserved phenomenon among all living organisms and a major veritable public health problem worldwide. Repetitive uses of antibiotics lead to antimicrobial drug resistance. Here, 19,20-epoxycytochalasin Q (ECQ) was isolated from endophytic fungus Xylaria sp. BCC 1067 and, its chemical structure was determined via chromatographic and spectral methods. ECQ displayed an antifungal activity with low MIC₅₀ of 410 and 55 mg/l in the model yeast Saccharomyces cerevisiae wild-type and ScΔpdr5 strains, respectively. ECQ was a new inducer and potential substrate of key multi-drug efflux pumps S. cerevisiae ScPdr5 and Candida albicans CaCdr1. ECQ targeted actin filament, disrupting actin dynamics of yeast cells. ECQ also sensitized the ScΔsrv2 mutant, lacking suppressor of RasVal19. Overexpression of ScPDR5 or CaCDR1 genes prevented aggregation of actin and alleviated antifungal effect of ECQ. Additionally, ECQ induced high accumulation of reactive oxygen species, caused plasma membrane leakage and decreased yeast cell survival. Importantly, a discovery of ECQ implied a cellular connection between multi-drug resistance and actin stability, an important determinant of transporter mediated-drug resistance mechanism. Combination of ECQ and antifungal azoles displayed promising drug synergy against S. cerevisiae strains expressing multi-drug transporters, thereby providing potential solution for antifungal therapy and chemotherapeutic application.

在所有活生物体中，多药耐药性是高度保守的现象，也是全球范围内真正的主要公共卫生问题。重复使用抗生素会导致抗药性。在这里，从内生真菌Xylaria sp。分离出19,20-环氧细胞松弛素Q（ECQ）。BCC 1067及其化学结构是通过色谱和光谱法确定的。ECQ显示的抗真菌活性与低MIC ₅₀ 410和55毫克/升在模型酵母酿酒酵母野生型和钪Δ PDR5分别菌株。ECQ是关键的多种药物外排泵S.cerevisiae Sc Pdr5和白色念珠菌Ca的新诱导剂和潜在底物Cdr1。ECQ靶向肌动蛋白丝，破坏酵母细胞的肌动蛋白动力学。ECQ也致敏的钪Δ SRV2突变，缺乏RasVal19的抑制。ScPDR5或CaCDR1基因的过表达阻止肌动蛋白的聚集并减轻ECQ的抗真菌作用。另外，ECQ引起活性氧的大量积累，导致质膜泄漏并降低了酵母细胞的存活率。重要的是，ECQ的发现暗示了多种药物抗性和肌动蛋白稳定性之间的细胞联系，肌动蛋白稳定性是转运蛋白介导的药物抗性机制的重要决定因素。ECQ和抗真菌唑类药物的组合显示出抗啤酒酵母的协同作用 表达多种药物转运蛋白的菌株，从而为抗真菌治疗和化学治疗应用提供了潜在的解决方案。