Dižová S, Bujdáková H
Pharmazie. 2017 Jun 1;72(6):307-312. doi: 10.1691/ph.2017.6174.
Farnesol is a quorum sensing (QS) molecule synthesized by Candida albicans acting as a negative regulator of morphogenesis; it blocks the yeast-to-hyphae transformation. This molecule is currently studied in particular from the viewpoint of possible use as a substance with anticancer properties and with an antimicrobial, and anti-biofilm effect in yeasts resistant or tolerant to conventional therapeutic agents, for example fluconazole. Besides the aforementioned effect on morphological transformation through cyclic AMP (cAMP)/protein kinase A (cAMP-PKA) pathway, it also affects other biochemical pathways of yeasts, for example those ones for sterol biosynthesis or triggering of apoptosis via accumulation of ROS (reactive oxygen species) that damage essential cellular compartments. ROS activate intracellular caspases that are indicators of apoptotic response in C. albicans. However, an influence of farnesol on C. albicans yeasts is dependent on used concentrations; while higher concentrations (200 - 300 μM) are stressful for yeasts, lower concentrations (about 40 μM) protect them from stress. This QS molecule is also able to modulate efflux pumps in resistant yeasts. This review provides an overview of the current knowledge about production, role, and mode of action of farnesol in the clinically most important yeast C. albicans.
法尼醇是一种由白色念珠菌合成的群体感应(QS)分子,作为形态发生的负调节因子;它能阻止酵母向菌丝的转变。目前对该分子的研究,尤其着眼于其作为一种具有抗癌特性、对耐常规治疗药物(如氟康唑)的酵母具有抗菌和抗生物膜作用的物质的潜在用途。除了上述通过环磷酸腺苷(cAMP)/蛋白激酶A(cAMP-PKA)途径对形态转变产生的影响外,它还会影响酵母的其他生化途径,例如甾醇生物合成途径或通过活性氧(ROS)的积累引发细胞凋亡,ROS会损害重要的细胞区室。ROS激活细胞内的半胱天冬酶,这些酶是白色念珠菌凋亡反应的指标。然而,法尼醇对白色念珠菌酵母的影响取决于所使用的浓度;较高浓度(200 - 300 μM)对酵母具有应激作用,而较低浓度(约40 μM)则能保护它们免受应激。这种QS分子还能够调节耐药酵母中的外排泵。本综述概述了目前关于法尼醇在临床上最重要的酵母——白色念珠菌中的产生、作用和作用方式的知识。