Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump
Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump
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DOI：
10.1111/j.1365-2672.2007.03617.x
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Lou, H. -X.
中科院分区：
文献类型：
--
作者：
Guo, X. -L.;Leng, P.;Lou, H. -X.
目标：在这项研究中，我们调查的效果plagiochin E（PLE），一种植物衍生的酚类天然产物，在体外对真菌耐药性的逆转氟康唑（FLC）和相关mechanism.Methods和结果：PLE和FLC的协同作用，观察到在FLC耐药的白色念珠菌菌株，并进行了评价使用分数抑制浓度指数。在耐FLC的C.采用液相色谱-串联质谱法测定rh 123对白念珠菌细胞外排的影响，并通过测定Rh 123的外排量来评价rh 123对白念珠菌细胞外排的影响。PLE显着抑制外排，但不吸收，Rh 123在FLC-耐药菌株在磷酸盐缓冲液与5%葡萄糖。多药耐药基因CDR 1在FLC耐药株中的过表达。结论：PLE可通过抑制FLC的外排逆转真菌对FLC的耐药性。本研究的意义和影响：本研究结果表明，PLE和FLC联合应用可能为临床治疗FLC耐药菌株引起的真菌感染提供一种途径。
Aim: In this study, we investigated the effect of plagiochin E (PLE), a botanic-derived phenolic natural product, on reversal of fungal resistance to fluconazole (FLC) in vitro and the related mechanism.Methods and Results: A synergistic action of PLE and FLC was observed in the FLC-resistant Candida albicans strains and was evaluated using the fractional inhibited concentration index. The effect of PLE on FLC intracellular uptake was investigated in FLC-resistant C. albicans cells by liquid chromatography-tandem mass spectrometry, and the effect on efflux drug pump was assessed by measuring the efflux of Rhodamine 123 (Rh123). PLE significantly inhibited the efflux, but not the absorption, of Rh123 in FLC-resistant strains in phosphate-buffered saline with 5% glucose. Overexpression of the multidrug-resistance gene CDR1 in FLC-resistant C. albicans isolates was detected, and the introduction of PLE to the cells showed a significant reduction of the CDR1 expression in those FLC-resistant isolates.Conclusions: These findings indicate that PLE could reverse the fungal resistant to FLC by inhibiting the efflux of FLC from C. albicans, and this effect may be related to the efflux pump.Significance and Impact of the Study: These results indicate that the combination of PLE and FLC may provide an approach for the clinical therapy of fungus infection induced by FLC-resistant strains.