氟康唑通过抑制细胞麦角固醇合成来与小檗碱协同作用，对抗酵母菌。
Fluconazole inhibits cellular ergosterol synthesis to confer synergism with berberine against yeast cells.
机构信息
Key Lab of Eco-Textile (Ministry of Education), College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 Renmin Road, Shanghai 201620, PR China.
Shanghai Key Laboratory of Crime Scene Evidence, Shanghai Research Institute of Criminal Science and Technology, Zhongshan North No. 1 Road, Shanghai 200083, PR China.
出版信息
J Glob Antimicrob Resist. 2018 Jun;13:125-130. doi: 10.1016/j.jgar.2017.12.011. Epub 2017 Dec 26.
OBJECTIVES
Although berberine (BBR) is reported to exhibit weak activity against Candida albicans, combined use of BBR and fluconazole (FLC) showed synergism against FLC-resistant C. albicans in vitro. The aim of this study was to explore the synergistic antifungal mechanism of FLC and BBR in Saccharomyces cerevisiae, a typical fungal cell model.
METHODS
Biochemical and genetic analyses were performed to investigate the probable antifungal role of the combined use of BBR and FLC in S. cerevisiae.
RESULTS
FLC led to elevated cell membrane permeability in the wild-type S. cerevisiae BY4741, similar to the sterol synthesis-deficient strains erg2Δ and erg6Δ. Biochemical analysis indicated that FLC significantly inhibited cellular ergosterol synthesis, leading to a decrease in cell membrane stability, which increased the rate of BBR uptake and utilisation and reduced the inhibitory concentrations of BBR in wild-type yeast cells. Genetic analysis of the inhibitory effect of FLC and BBR on sterol synthesis-deficient (erg2Δ and erg6Δ) and DNA damage repair defect (rad1Δ) strains showed that FLC and BBR possess different antifungal mechanisms.
CONCLUSIONS
FLC enhances cell membrane permeability via inhibition of cellular ergosterol synthesis, thus assisting BBR to kill fungal cells.
目的
尽管小檗碱（BBR）对白色念珠菌的活性较弱，但 BBR 与氟康唑（FLC）联合使用时显示出体外抗氟康唑耐药白色念珠菌的协同作用。本研究旨在探讨 BBR 和 FLC 在酿酒酵母（一种典型的真菌细胞模型）中的协同抗真菌机制。
方法
采用生化和遗传分析方法研究 BBR 和 FLC 联合使用在酿酒酵母中的可能抗真菌作用。
结果
FLC 导致野生型酿酒酵母 BY4741 的细胞膜通透性增加，类似于甾醇合成缺陷菌株 erg2Δ 和 erg6Δ。生化分析表明，FLC 显著抑制细胞内麦角固醇合成，导致细胞膜稳定性降低，这增加了 BBR 的摄取和利用速率，并降低了野生型酵母细胞中 BBR 的抑制浓度。对甾醇合成缺陷（erg2Δ 和 erg6Δ）和 DNA 损伤修复缺陷（rad1Δ）菌株中 FLC 和 BBR 抑制甾醇合成的抑制作用进行遗传分析表明，FLC 和 BBR 具有不同的抗真菌机制。
结论
FLC 通过抑制细胞内麦角固醇合成来增加细胞膜通透性，从而协助 BBR 杀死真菌细胞。
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