Department of Biotransformation, Faculty of Biotechnology, University of Wrocław, 50-383 Wrocław, Poland.
Int J Mol Sci. 2021 Feb 21;22(4):2127. doi: 10.3390/ijms22042127.
is a pathogenic fungus that is increasingly developing multidrug resistance (MDR), including resistance to azole drugs such as fluconazole (FLC). This is partially a result of the increased synthesis of membrane efflux transporters Cdr1p, Cdr2p, and Mdr1p. Although all these proteins can export FLC, only Cdr1p is expressed constitutively. In this study, the effect of elevated fructose, as a carbon source, on the MDR was evaluated. It was shown that fructose, elevated in the serum of diabetics, promotes FLC resistance. Using strains with green fluorescent protein (GFP) tagged MDR transporters, it was determined that the FLC-resistance phenotype occurs as a result of Mdr1p activation and via the increased induction of higher Cdr1p levels. It was observed that fructose-grown cells displayed a high efflux activity of both transporters as opposed to glucose-grown cells, which synthesize Cdr1p but not Mdr1p. Additionally, it was concluded that elevated fructose serum levels induce the de novo production of Mdr1p after 60 min. In combination with glucose, however, fructose induces Mdr1p production as soon as after 30 min. It is proposed that fructose may be one of the biochemical factors responsible for Mdr1p production in cells.
是一种致病真菌，它越来越多地产生多药耐药性（MDR），包括对氟康唑（FLC）等唑类药物的耐药性。这部分是由于膜外排转运蛋白 Cdr1p、Cdr2p 和 Mdr1p 的合成增加所致。尽管所有这些蛋白质都可以输出 FLC，但只有 Cdr1p 是组成型表达的。在这项研究中，评估了升高的果糖（作为碳源）对 MDR 的影响。结果表明，糖尿病患者血清中升高的果糖促进了 FLC 耐药性。使用标记有绿色荧光蛋白（GFP）的 MDR 转运蛋白的菌株，确定 FLC 耐药表型是由于 Mdr1p 的激活以及更高水平的 Cdr1p 的诱导增加所致。结果观察到，与葡萄糖生长的细胞相比，果糖生长的细胞表现出两种转运蛋白的高外排活性，葡萄糖生长的细胞合成 Cdr1p 但不合成 Mdr1p。此外，还得出结论，升高的果糖血清水平在 60 分钟后诱导 Mdr1p 的从头产生。然而，与葡萄糖结合时，果糖在 30 分钟后即可诱导 Mdr1p 的产生。因此，推测果糖可能是导致细胞中 Mdr1p 产生的生化因素之一。
