Mahendrarajan Venkatramanan, Bari Vinay Kumar
Department of Biochemistry, School of Basic Sciences, Central University of Punjab, VPO-Ghudda, Bathinda, India.
Mycology. 2022 Oct 28;13(4):305-317. doi: 10.1080/21501203.2022.2138599. eCollection 2022.
and its related species can cause opportunistic infections such as "candidiasis" in immunocompromised individuals with a high morbidity and mortality rate. Several antifungal drugs available in the market are often used to treat infections caused by pathogenic fungi. However, in fungi, the development of resistance against these drugs quickly evolved. is a dimorphic fungus that can switch between yeast to hyphae form, requires an active biosynthesis of membrane constituents. Sphingolipid and ergosterol molecules, are the major fungal plasma membrane components, and their interaction with the antifungal drug can modulate drug susceptibility. A lipophilic compound farnesol acts as a quorum-sensing molecule synthesised by the isoprenoid biosynthesis pathway in the fungal pathogen . Farnesol is secreted in a cell density-dependent manner inhibits hyphae germination and biofilm formation. In this study, we have investigated whether the farnesol molecules affect the drug susceptibility of the antifungal drug Amphotericin B (AmB) which mainly binds with ergosterol, and Aureobasidin A (AbA), a complex sphingolipid biosynthesis inhibitor. Our studies revealed that a non-toxic and low concentration of farnesol can reduce the efficacy of AmB and AbA on yeast cells. This reduction is probably through the alteration in the complex sphingolipid biosynthesis and ATP-binding cassette (ABC) type membrane transport activity. These findings may shed light on a new direction to explore the role of lipid molecules in the antifungal drug resistance mechanisms in pathogenic yeast.
及其相关物种可在免疫功能低下的个体中引起机会性感染，如“念珠菌病”，发病率和死亡率很高。市场上有几种抗真菌药物常用于治疗由致病真菌引起的感染。然而，在真菌中，对这些药物的耐药性发展迅速。是一种双态真菌，可在酵母形态和菌丝形态之间转换，需要活跃的膜成分生物合成。鞘脂和麦角固醇分子是真菌质膜的主要成分，它们与抗真菌药物的相互作用可调节药物敏感性。亲脂性化合物法尼醇作为一种群体感应分子，由真菌病原体中的类异戊二烯生物合成途径合成。法尼醇以细胞密度依赖性方式分泌，抑制菌丝萌发和生物膜形成。在本研究中，我们研究了法尼醇分子是否会影响主要与麦角固醇结合的抗真菌药物两性霉素B（AmB）以及鞘脂生物合成复杂抑制剂金担子素A（AbA）的药物敏感性。我们的研究表明，无毒且低浓度的法尼醇可降低AmB和AbA对酵母细胞的疗效。这种降低可能是通过鞘脂生物合成和ATP结合盒（ABC）型膜转运活性的改变实现的。这些发现可能为探索脂质分子在致病酵母抗真菌耐药机制中的作用提供一个新方向。
