Thibane Vuyisile S, Ells Ruan, Hugo Arno, Albertyn Jacobus, van Rensburg Walter J Janse, Van Wyk Pieter W J, Kock Johan L F, Pohl Carolina H
Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, P. O. Box 339, Bloemfontein, 9300, South Africa.
Biochim Biophys Acta. 2012 Oct;1820(10):1463-8. doi: 10.1016/j.bbagen.2012.05.004. Epub 2012 May 17.
Polyunsaturated fatty acids (PUFAs) have antifungal properties, but the mode by which they induce their action is not always clear. The aim of the study was to investigate apoptosis as a mode of action of antifungal PUFAs (stearidonic acid, eicosapentaenoic acid and docosapentaenoic acid) which are inhibitory towards biofilm formation of C. albicans and C. dubliniensis.
Candida biofilms were grown in the absence or presence of 1mM PUFAs (linoleic acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid) for 48h at 37°C. The effect of these PUFAs on the membrane fatty acid profile and unsaturation index, oxidative stress, mitochondrial transmembrane potential and apoptosis was evaluated.
When biofilms of C. albicans and C. dubliniensis were exposed to certain PUFAs there was an increase in unsaturation index of the cellular membranes and accumulation of intracellular reactive oxygen species (ROS). This resulted in apoptosis, evidenced by reduced mitochondrial membrane potential and nuclear condensation and fragmentation. The most effective PUFA was stearidonic acid.
The resultant cell death of both C. albicans and C. dubliniensis is due to apoptosis.
Due to the increase in drug resistance, alternative antifungal drugs are needed. A group of natural antifungal compounds is PUFAs. However, understanding their mechanisms of action is important for further use and development of these compounds as antifungal drugs. This paper provides insight into a possible mode of action of antifungal PUFAs.
多不饱和脂肪酸(PUFAs)具有抗真菌特性,但其作用方式并不总是明确。本研究旨在探讨细胞凋亡作为抗真菌PUFAs(十八碳四烯酸、二十碳五烯酸和二十二碳五烯酸)的一种作用方式,这些PUFAs对白色念珠菌和都柏林念珠菌的生物膜形成具有抑制作用。
念珠菌生物膜在不存在或存在1mM PUFAs(亚油酸、十八碳四烯酸、二十碳五烯酸、二十二碳五烯酸)的情况下于37°C培养48小时。评估了这些PUFAs对膜脂肪酸谱和不饱和度指数、氧化应激、线粒体跨膜电位和细胞凋亡的影响。
当白色念珠菌和都柏林念珠菌的生物膜暴露于某些PUFAs时,细胞膜的不饱和度指数增加,细胞内活性氧(ROS)积累。这导致了细胞凋亡,表现为线粒体膜电位降低以及细胞核凝聚和碎片化。最有效的PUFA是十八碳四烯酸。
白色念珠菌和都柏林念珠菌最终的细胞死亡是由于细胞凋亡。
由于耐药性增加,需要替代抗真菌药物。一类天然抗真菌化合物是PUFAs。然而,了解它们的作用机制对于这些化合物作为抗真菌药物的进一步应用和开发很重要。本文深入探讨了抗真菌PUFAs可能的作用方式。