PDF(Pubmed)
Abstract：
Host recognition of the pathogen-associated molecular pattern (PAMP), β-1,3-glucan, plays a major role in antifungal immunity. β-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen Candida albicans. Most β-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface. In response to host signals such as lactate, C. albicans shaves the exposed β-1,3-glucan from its cell surface, thereby reducing the ability of innate immune cells to recognise and kill the fungus. We have used sets of barcoded xog1 and eng1 mutants to compare the impacts of the secreted β-glucanases Xog1 and Eng1 upon C. albicans in vitro and in vivo. Flow cytometry of Fc-dectin-1-stained strains revealed that Eng1 plays the greater role in lactate-induced β-1,3-glucan masking. Transmission electron microscopy and stress assays showed that neither Eng1 nor Xog1 are essential for cell wall maintenance, but the inactivation of either enzyme compromised fungal adhesion to gut and vaginal epithelial cells. Competitive barcode sequencing suggested that neither Eng1 nor Xog1 strongly influence C. albicans fitness during systemic infection or vaginal colonisation in mice. However, the deletion of XOG1 enhanced C. albicans fitness during gut colonisation. We conclude that both Eng1 and Xog1 exert subtle effects on the C. albicans cell surface that influence fungal adhesion to host cells and that affect fungal colonisation in certain host niches.
摘要：
病原体相关分子模式（PAMP）的宿主识别，β-1,3-葡聚糖,在抗真菌免疫中起主要作用。β-1,3-葡聚糖是机会性病原体白色念珠菌的内细胞壁的必需成分。大多数β-1,3-葡聚糖被甘露聚糖原纤维的外细胞壁层屏蔽，但有些会暴露在细胞表面。响应宿主信号，如乳酸，白色念珠菌从其细胞表面刮掉暴露的β-1,3-葡聚糖，从而降低先天免疫细胞识别和杀死真菌的能力。我们已经使用条形码xog1和eng1突变体组来比较分泌的β-葡聚糖酶Xog1和Eng1在体外和体内对白色念珠菌的影响。Fc-dectin-1染色菌株的流式细胞术显示，Eng1在乳酸诱导的β-1,3-葡聚糖掩蔽中起着更大的作用。透射电子显微镜和应力分析显示，Eng1和Xog1都不是细胞壁维持所必需的，但是两种酶的失活都会损害真菌对肠道和阴道上皮细胞的粘附。竞争性条形码测序表明Eng1和Xog1均不强烈影响小鼠中全身感染或阴道定植期间的白色念珠菌适应性。然而,XOG1的缺失增强了肠道定植期间的白色念珠菌适应性。我们得出的结论是，Eng1和Xog1都对白色念珠菌细胞表面产生微妙的影响，从而影响真菌对宿主细胞的粘附，并影响某些宿主生态位中的真菌定植。
