PDF(Pubmed)
Abstract：
Cellular membranes are essential for compartmentalization, maintenance of permeability, and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically bilayer-forming dialkyl glycerol diethers (DGDs) and monolayer-forming glycerol dialkyl glycerol tetraethers (GDGTs). The antifungal allylamine terbinafine has been proposed as an inhibitor of GDGT biosynthesis in archaea based on radiolabel incorporation studies. The exact target(s) and mechanism of action of terbinafine in archaea remain elusive. Sulfolobus acidocaldarius is a strictly aerobic crenarchaeon thriving in a thermoacidophilic environment, and its membrane is dominated by GDGTs. Here, we comprehensively analyzed the lipidome and transcriptome of S. acidocaldarius in the presence of terbinafine. Depletion of GDGTs and the accompanying accumulation of DGDs upon treatment with terbinafine were growth phase-dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, which resulted in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine has a multitude of effects, including significant differential expression of genes in the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization. Combined, these findings suggest that the response of S. acidocaldarius to terbinafine inhibition involves respiratory stress and the differential expression of genes involved in isoprenoid biosynthesis and saturation.
摘要：
细胞膜对于分隔是必不可少的，保持渗透性，以及生活中三个领域的流动性。古菌属于生命的第三领域，具有独特的磷脂组成。古细菌的膜脂质是醚连接的分子，特别是形成双层的二烷基甘油二醚（DGD）和形成单层的甘油二烷基甘油四醚（GDGT）。根据放射性标记掺入研究，已提出抗真菌烯丙胺特比萘芬作为古细菌中GDGT生物合成的抑制剂。特比萘芬在古细菌中的确切目标和作用机制仍然难以捉摸。Sulfolobusacidocaldarius是一种严格的需氧古细菌，在嗜酸性环境中蓬勃发展，它的膜以GDGTs为主。这里,在特比萘芬存在下，我们全面分析了S.acidocaldarius的脂质组和转录组。用特比萘芬处理后，GDGT的消耗和随之而来的DGD的积累是生长阶段依赖性的。此外,观察到钙的饱和度发生了重大变化，导致不饱和分子的积累。转录组数据表明特比萘芬具有多种作用，包括呼吸道复合体中基因的显著差异表达，运动性,细胞包膜,脂肪酸代谢，和GDGT环化。合并,这些发现表明,酸乳杆菌对特比萘芬抑制的反应涉及呼吸应激和类异戊二烯生物合成和饱和相关基因的差异表达.
