Suchodolski Jakub, Derkacz Daria, Muraszko Jakub, Panek Jarosław J, Jezierska Aneta, Łukaszewicz Marcin, Krasowska Anna
Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.
Faculty of Chemistry, University of Wroclaw, 50-383 Wroclaw, Poland.
Pharmaceutics. 2020 Apr 1;12(4):314. doi: 10.3390/pharmaceutics12040314.
Recognizing the -glucan component of the cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed -glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks -glucan when the cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with -glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.
识别细胞壁的β-葡聚糖成分是宿主免疫系统识别过程中涉及的必要步骤。能使免疫系统识别出暴露的β-葡聚糖的化合物可能是有价值的抗真菌药物。抗真菌药物的研发尤为重要，因为真菌的耐药性越来越强。本研究表明，当酵母细胞缺乏麦角固醇时，脂肽表面活性素会使β-葡聚糖暴露。当麦角固醇被氟康唑消耗时，这一观察结果同样成立。在氟康唑存在的情况下，表面活性素不会增强局部几丁质积累的作用。编码一种占细胞几丁质80%的基因产物的基因表达下调。酵母暴露于氟康唑会改变真菌质膜的组成和结构。与此同时，真菌细胞壁也会以一种使真菌易受表面活性素影响的方式发生改变和重塑。计算机模拟研究表明，表面活性素可与β-葡聚糖形成复合物。表面活性素与几丁质形成的复合物稳定性较差，再加上几丁质合成减少，这可能是这种脂肽的第二种抗真菌作用机制。
