Instituto de Ciencias Básicas-Laboratorio de Alta Tecnología de Xalapa (LATEX). Médicos, 5, Colonia Unidad del Bosque. CP 91010 Xalapa, Veracruz, México.
Mycologia. 2002 Jul-Aug;94(4):563-8. doi: 10.1080/15572536.2003.11833184.
Ergosterol is an important component of fungal membranes. This sterol can be easily transformed to peroxide of ergosterol by photo-oxidation with singlet oxygen. Cultures of Papalauspora immersa were grown on Czapeck agar medium, and subjected to the following conditions: 1) irradiation with daylight and quartz light (excluding UV light), 2) addition by diffusion of yellowish eosine (0.1 mg/mL), and 3) the control (no yellowish eosine, under darkness conditions). Fungal growth was completely inhibited after the treatment with quartz light (3 h) and yellow eosine, and no growth was observed in subsequent subcultures. These results suggested that plasma membrane components changed significantly by the transformation of ergosterol to peroxide of ergosterol leading to fungal death. To confirm this, a second experiment on a larger scale was carried out in which the fungus was grown on liquid medium in test tubes, treated, irradiated, and tested for peroxide of ergosterol by (1)HNMR. This peroxide was only found in treated samples. These findings represent a new strategy for developing antifungal agents, based on ergosterol photo-oxidation which might probably be related to the disruption of the plasma membrane, instead of only preventing the ergosterol biosynthesis. The potential application of this strategy for the selective control or prevention of pathogenic fungi is considerable.
麦角甾醇是真菌膜的重要组成部分。这种固醇很容易被单线态氧的光氧化转化为麦角甾醇过氧化物。将沉浸被孢霉接种到察氏琼脂培养基上,然后进行以下处理:1)用日光和石英光(不包括紫外线)照射,2)通过扩散添加黄色曙红(0.1mg/mL),3)对照(无黄色曙红,在黑暗条件下)。用石英光(3 小时)和黄色曙红处理后,真菌生长完全受到抑制,随后的继代培养中没有观察到生长。这些结果表明,麦角甾醇向麦角甾醇过氧化物的转化导致细胞膜成分发生显著变化,从而导致真菌死亡。为了证实这一点,进行了第二项更大规模的实验,在实验试管中用液体培养基培养真菌,进行处理、照射,并通过(1)HNMR 检测麦角甾醇过氧化物。仅在处理过的样品中发现了这种过氧化物。这些发现代表了一种新的抗真菌药物开发策略,基于麦角甾醇的光氧化,这可能与破坏质膜有关,而不仅仅是阻止麦角甾醇的生物合成。这种策略在选择性控制或预防致病性真菌方面具有很大的应用潜力。