Oguro Yoshifumi, Yamazaki Harutake, Takagi Masamichi, Takaku Hiroaki
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, 956-8603, Japan.
Curr Genet. 2014 May;60(2):89-97. doi: 10.1007/s00294-013-0416-8. Epub 2013 Nov 20.
An antifungal defensin, AFP1, of Brassica juncea inhibits the growth of various microorganisms. The molecular details of this inhibition remain largely unknown. Herein, we reveal that a specific structure of fungal sphingolipid glucosylceramide (GlcCer) is critical for the sensitivity of Candida albicans cells to AFP1. Our results revealed that AFP1 induces plasma membrane permeabilization and the production of reactive oxygen species (ROS) in wild-type C. albicans cells, but not in cells lacking the ninth methyl residue of the GlcCer sphingoid base moiety, which is a characteristic feature of fungi. AFP1-induced ROS production is responsible for its antifungal activity, with a consequent loss of yeast cell viability. These findings suggest that AFP1 specifically recognizes the structural difference of GlcCer for targeting of the fungal pathogens.
芥菜的一种抗真菌防御素AFP1可抑制多种微生物的生长。这种抑制作用的分子细节在很大程度上仍不清楚。在此，我们揭示真菌鞘脂葡萄糖神经酰胺（GlcCer）的特定结构对于白色念珠菌细胞对AFP1的敏感性至关重要。我们的结果表明，AFP1可诱导野生型白色念珠菌细胞的质膜通透性增加和活性氧（ROS）的产生，但在缺乏GlcCer鞘氨醇碱基部分第九个甲基残基的细胞中则不会，这是真菌的一个特征。AFP1诱导的ROS产生是其抗真菌活性的原因，随后酵母细胞活力丧失。这些发现表明，AFP1通过特异性识别GlcCer的结构差异来靶向真菌病原体。
