Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence

Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence
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DOI:
10.1128/ec.00370-07
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发表时间:
2008-01-01
期刊:
影响因子:
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通讯作者:
Casadevall, Arturo
Casadevall, Arturo
中科院分区:
其他
文献类型:
--
作者:
Rodrigues, Marcio L.;Nakayasu, Ernesto S.;Casadevall, Arturo

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新型隐球菌产生的囊泡含有其主要的毒力因子,荚膜多糖葡糖醛酸甘露聚糖(GXM)。这些囊泡穿过细胞壁到达细胞外空间,在那里多糖被认为用于囊生长或递送到宿主组织中。在本研究中,我们的特点囊泡形态和蛋白质组成的组合技术,包括电子显微镜,蛋白质组学,酶活性和血清学反应。分泌囊泡在C. neoformans似乎与来源于多泡体的外来体样区室相关。细胞外囊泡的大小和形态各异,包括电子透明膜体和电子致密囊泡。通过蛋白质组学分析鉴定了76种蛋白质,包括几种与毒性和抗氧化应激相关的蛋白质。生化试验表明,漆酶和尿素酶活性的囊泡。此外,不同的囊泡蛋白被隐球菌病患者的血清所识别。这些结果揭示了C.这表明细胞外囊泡作为“毒力袋”发挥作用,将真菌产物的浓缩有效载荷递送至宿主效应细胞和组织。
Cryptococcus neoformans produces vesicles containing its major virulence factor, the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. In the present study, we characterized vesicle morphology and protein composition by a combination of techniques including electron microscopy, proteomics, enzymatic activity, and serological reactivity. Secretory vesicles in C. neoformans appear to be correlated with exosome-like compartments derived from multivesicular bodies. Extracellular vesicles manifested various sizes and morphologies, including electron-lucid membrane bodies and electron-dense vesicles. Seventy-six proteins were identified by proteomic analysis, including several related to virulence and protection against oxidative stress. Biochemical tests indicated laccase and urease activities in vesicles. In addition, different vesicle proteins were recognized by sera from patients with cryptococcosis. These results reveal an efficient and general mechanism of secretion of pathogenesis-related molecules in C. neoformans, suggesting that extracellular vesicles function as "virulence bags" that deliver a concentrated payload of fungal products to host effector cells and tissues.