关键词: Candida albicans Sur7 extracellular vesicles virulence

来  源:   DOI:10.1002/jex2.82   PDF(Pubmed)

Abstract:
Extracellular vesicles (EVs) from human fungal pathogens have been implicated in fungal virulence, yet little is known about their role in the host-pathogen interaction. Progress has been hampered by the lack of a specific marker for fungal EVs that can be used to monitor EV isolation and tracking in biological systems. Here we report the effect of a SUR7 gene knockout on the production, properties, and role of EVs in the virulence of Candida albicans. Sur7 is a component of the membrane compartment of Can1 (MCC) complex and is enriched in the EVs from C. albicans and other fungal species. MCC is a plasma membrane complex which together with the eisosome, a cytoplasmic protein complex, is a key regulator in plasma membrane organisation and plasma membrane associated processes. The SUR7 knockout strain produces smaller EVs than the wild-type (WT) with different protein and carbohydrate cargos. Furthermore, proteins with known roles in Candida pathogenesis were present in WT EVs and absent or diminished in the sur7Δ EVs. We demonstrate that the reduced virulence of the sur7Δ cells can be partially restored with EVs from a WT strain. These findings demonstrate the importance of Sur7-like proteins in the biogenesis of EVs in fungi and enhance our understanding of the role of fungal EVs in human pathogenesis.
摘要:
来自人类真菌病原体的细胞外囊泡(EV)与真菌毒力有关,然而,对它们在宿主-病原体相互作用中的作用知之甚少。由于缺乏可用于监测生物系统中的EV分离和跟踪的真菌EV的特定标记,因此进展受到阻碍。在这里,我们报告了SUR7基因敲除对生产的影响,属性,以及电动汽车在白色念珠菌毒力中的作用。Sur7是Can1(MCC)复合物的膜隔室的组分,并且富集在来自白色念珠菌和其他真菌物种的EV中。MCC是一种质膜复合物,与eisosome一起,细胞质蛋白复合物,是质膜组织和质膜相关过程的关键调节剂。SUR7敲除菌株产生比具有不同蛋白质和碳水化合物货物的野生型(WT)更小的EV。此外,在念珠菌发病机制中具有已知作用的蛋白质存在于WTEV中,而在sur7ΔEV中缺失或减少。我们证明,sur7Δ细胞的毒力降低可以用WT菌株的EV部分恢复。这些发现证明了Sur7样蛋白在真菌中EV生物发生中的重要性,并增强了我们对真菌EV在人类发病机理中的作用的理解。
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