The secretory Candida effector Sce1 licenses fungal virulence by masking the immunogenic β-1,3-glucan and promoting apoptosis of the host cells
The secretory Candida effector Sce1 licenses fungal virulence by masking the immunogenic β-1,3-glucan and promoting apoptosis of the host cells
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DOI：
10.1002/mlf2.12066
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发表时间：
2023-06-01
期刊：
影响因子：
--
通讯作者：
Chen，Jiangye
中科院分区：
文献类型：
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作者：
Wu，Hongyu;Wang，Li;Chen，Jiangye
白念珠菌通过形态转换、诱导子释放等多种机制增强其致病力。然而，真菌和宿主之间复杂的相互作用仍然知之甚少，真菌毒力因子的全面清单尚未建立。在这项研究中，我们确定了一个C。白色念珠菌分泌效应蛋白Sce 1，其诱导和分泌与阴道模拟条件和厚垣孢子形成相关。序列比对表明Sce 1属于C.白色念珠菌，其在几种真菌中是保守的，并且主要表征为酿酒酵母中的β-葡聚糖结合蛋白。在机械上，Sce 1主要以切割形式定位于细胞壁，作为碱不稳定的β-1，3-葡聚糖结合蛋白，并在酸性环境和厚垣孢子中掩蔽β-葡聚糖中发挥作用，这可能是C的特征。白色念珠菌逃避宿主免疫的能力此外，切割的短形式的Sce 1蛋白可以释放到细胞外区室中，并在感染厚垣孢子的骨髓源性巨噬细胞中呈递。这种切割的短形式的Sce 1也证明了在各种宿主细胞中触发半胱天冬酶-8/9依赖性凋亡的独特能力。相应地，SCE 1基因缺失导致阴道定植C.在全身感染过程中，白色念珠菌和真菌毒力降低。Sce 1作为一种多功能的毒力效应子，在不同的区室执行的发现揭示了真菌-宿主相互作用和C。白色孢子发生
Candida albicansdeploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence. However, the intricate interactions between the fungus and the host remain poorly understood, and a comprehensive inventory of fungal virulence factors has yet to be established. In this study, we identified aC. albicanssecretory effector protein Sce1, whose induction and secretion are associated with vagina‐simulative conditions and chlamydospore formation. Sequence alignment showed that Sce1 belongs to a Pir family inC. albicans, which is conserved across several fungi and primarily characterized as a β‐glucan binding protein in theSaccharomyces cerevisiae. Mechanically, Sce1 is primarily localized to the cell wall in a cleaved form as an alkali‐labile β‐1,3‐glucan binding protein and plays a role in masking β‐glucan in acidic environments and chlamydospores, a feature that might underlineC. albicans' ability to evade host immunity. Further, a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow‐derived macrophages infected with chlamydospores. This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases‐8/9‐dependent apoptosis in various host cells. Correspondingly, genetic deletion ofSCE1led to dampened vaginal colonization ofC. albicansand diminished fungal virulence during systemic infection. The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus–host interactions andC. albicanspathogenesis.