The Effect of Plagiochin E Alone and in Combination with Fluconazole on the Ergosterol Biosynthesis of Candida albicans(Microbiology)

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Plagiochin E (PLE), a macrocyclic bis (bibenzyl) isolated from the liverwort Marchantia polymorpha, has been reported to have antifungal activity and resistance reversal effects on Candida albicans. In order to understand the underlying mechanisms, we studied the effects of PLE alone and in combination with fluconazole (FLC) on the ergosterol biosynthetic pathway against both FLC-sensitive and FLC-resistant strains by analyzing the sterol content and the ergosterol pathway gene (ERG) expression. Relative quantitative analysis of different ergosterol precursors was carried out by employing the hyphenated technique of gas chromatography-high resolution mass spectrometry (GC-HR-MS). We observed that for FLC-resistant strain PLE itself can cause the accumulation of lanosterol and the decrease of 14α-methylfecosterol. When it combined with FLC, a significant decrease was observed in ergosterol formation and corresponding accumulation of 14α-methylated sterols was also found. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the transcription level of ERG11 was decreased in FLC-resistant strain when exposed to PLE alone or PLE plus FLC. These results suggest that PLE potentiates FLC antifungal activity by interfering with the FLC-targeted ergosterol biosynthesis pathway.
公益社団法人日本薬学会の論文
2009-01-01