侵袭性曲霉病对免疫功能低下的患者构成重大威胁,导致与这些感染相关的高死亡率。靶向细胞壁碳水化合物的生物合成是抗真菌药物开发的有希望的策略,并且将通过对细胞环境中多糖的天然结构的分子水平理解来推进。固态NMR光谱最近提供了有关烟曲霉细胞壁组织的详细见解,但是遗传和生化证据强调了曲霉物种之间的物种特异性差异。在这项研究中,我们使用了13C的组合,15N,和1H检测固态核磁共振,动态核极化(DNP),比较细胞壁聚合物的结构组织及其在烟曲霉和Nidulans细胞壁中的组装,两者都是关键的模式生物和人类病原体。这两个物种表现出相似的刚性核心结构,由几丁质组成,α-葡聚糖,和β-葡聚糖,这有助于类似的细胞壁特性,包括聚合物动力学,保水,和超分子组织。然而,在甲壳素中观察到差异,氨基半乳聚糖,蛋白质,和脂质含量,以及半乳甘露聚糖的动力学和葡聚糖基质的结构。
Invasive aspergillosis poses a significant threat to immunocompromised patients, leading to high mortality rates associated with these infections. Targeting the biosynthesis of cell wall carbohydrates is a promising strategy for antifungal drug development and will be advanced by a molecular-level understanding of the native structures of polysaccharides within their cellular context. Solid-state NMR spectroscopy has recently provided detailed insights into the cell wall organization of Aspergillus fumigatus, but genetic and biochemical evidence highlights species-specific differences among Aspergillus species. In this study, we employed a combination of 13C, 15N, and 1H-detection solid-state NMR, supplemented by Dynamic Nuclear Polarization (DNP), to compare the structural organization of cell wall polymers and their assembly in the cell walls of A. fumigatus and A. nidulans, both of which are key model organisms and human pathogens. The two species exhibited a similar rigid core architecture, consisting of chitin, α-glucan, and β-glucan, which contributed to comparable cell wall properties, including polymer dynamics, water retention, and supramolecular organization. However, differences were observed in the chitin, galactosaminogalactan, protein, and lipid content, as well as in the dynamics of galactomannan and the structure of the glucan matrix.