PDF(Pubmed)
Abstract：
Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length-scale corresponding to 3 to 4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.
摘要：
新生隐球菌是一种真菌病原体，可在免疫功能低下的个体中引起危及生命的脑部感染。与其他真菌病原体不同，它具有保护性多糖胶囊对其毒力至关重要。在感染期间,隐球菌细胞释放大量的细胞外多糖(exo-PS),其干扰宿主免疫应答。exo-PS和capsular-PS在隐球菌感染中至关重要，代表疾病诊断和疫苗开发策略的关键目标。然而,理解它们的结构因它们的多分散性而变得复杂，复杂性，对样品分离和处理的敏感性以及缺乏能够分离和分析它们同时保留其天然结构的方法。在这项研究中,我们首次使用小角度中子散射（SANS）和超小角度中子散射（USANS）来研究溶液中的真菌细胞悬浮液和细胞外多糖。我们的数据表明，溶液中的exo-PS表现出塌陷的链状行为和质量分形特性，这意味着在不同放大倍数下重复出现的重复模式或结构。多糖的局部结构表征为对应于3至4个重复单元的标度长度上的刚性杆。这项研究不仅揭示了对exo-PS和capsular-PS结构的见解，而且还证明了USANS在研究细胞尺寸变化以及未来中子散射研究中对比度变化的潜力。
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