School of Pharmaceutical Sciences, Shandong University, Jinan, China.
J Appl Microbiol. 2010 Jan;108(1):341-8. doi: 10.1111/j.1365-2672.2009.04429.x.
To clarify the underlying synergistic antifungal mechanisms of retigeric acid B (RAB) in combination with azoles against Candida albicans.
Increased accumulation of rhodamine 123 in C. albicans was measured by both spectrophotometric method and flow cytometry. The inhibitory properties to the drug efflux of C. albicans were determined spectrophotometrically. The decreased cellular ergosterol synthesis was measured using its unique spectrophotometric absorbance profile, and the downregulation expression levels of CDR1 and ERG11 were detected by real-time reverse transcription polymerase chain reaction. Transmission electron microscopy investigation found the wrinkled cell membrane and the impaired cell wall.
RAB synergizes the antifungal effect of azoles against C. albicans by inhibiting efflux pump activity, targeting the ergosterol biosynthesis pathway and increasing the fluidity for the resulted ergosterol depletion.
Investigating the mechanism of the synergy between RAB and azoles against C. albicans will help us to uncover the antifungal roles of this lichen-derived triterpene acid and find its possible clinical applications in overcoming fungal resistance.
阐明虎杖酸 B（RAB）与唑类药物联合抗白念珠菌的潜在协同抗真菌机制。
通过分光光度法和流式细胞术测量了罗丹明 123 在白念珠菌中的积累增加。通过分光光度法测定了对白念珠菌药物外排的抑制特性。使用其独特的分光光度吸收曲线测量了细胞麦角固醇合成的减少，并通过实时逆转录聚合酶链反应检测了 CDR1 和 ERG11 的下调表达水平。透射电子显微镜研究发现细胞膜起皱和细胞壁受损。
RAB 通过抑制外排泵活性、靶向麦角固醇生物合成途径和增加由于麦角固醇耗竭而导致的流动性，与唑类药物协同增强对白念珠菌的抗真菌作用。
研究 RAB 与唑类药物联合抗白念珠菌的协同作用机制将有助于我们揭示这种来源于地衣的三萜酸的抗真菌作用，并找到其在克服真菌耐药性方面的可能临床应用。
