Antifungal Activity of Mammalian Serum amyloid A1 against Candida albicans

Human serum amyloid A (SAA) is a major acute phase protein and shows a massive increase of concentration in plasma during inflammation. In the current study, we report that recombinant human and mouse SAA1 (rhSAA1 and rmSAA1) have a potent antifungal activity against the major fungal pathogen Candida albicans. rhSAA1 binds to the cell surface of C. albicans and promotes cell aggregation. At high concentrations, rhSAA1 disrupts the membrane integrity and induces rapid cell death of C. albicans. Further investigation demonstrates that rhSAA1 targets on the cell wall adhesin Als3 of C. albicans. Inactivation of ALS3 in C. albicans leads to remarkably decreased cell aggregation and death upon rhSAA1 treatment, implying that Als3 plays a critical role in SAA1 sensing. Moreover, deletion of the ALS3 transcriptional regulators such as AHR1, BCR1, and EFG1 in C. albicans results in a similar effect on cell responses to that of the als3/als3 mutant upon rhSAA1 treatment. Global gene expression profiling analysis indicates that rhSAA1 has a remarkable impact on the expression of cell wall- and metabolism-related genes in C. albicans. Our finding of the antifungal activity of rhSAA1 against C. albicans expands the function of this protein and would provide new insights into the understanding of the host-Candida interaction during infections. total RNA profiles of Candida albicans treated with SAA1 and PBS

人血清淀粉样蛋白A（Human serum amyloid A, SAA）是一类主要的急性期蛋白，在机体发生炎症时其血浆浓度会出现显著升高。本研究发现，重组人源SAA1（recombinant human SAA1, rhSAA1）与重组鼠源SAA1（recombinant mouse SAA1, rmSAA1）对主要致病真菌白色念珠菌（Candida albicans）具有强效抗真菌活性。rhSAA1可结合白色念珠菌的细胞表面并促进细胞聚集；在高浓度条件下，rhSAA1能够破坏真菌细胞膜完整性并诱导其快速死亡。进一步研究表明，rhSAA1的作用靶点为白色念珠菌的细胞壁黏附素Als3。将白色念珠菌的ALS3基因失活后，其在rhSAA1处理下的细胞聚集与死亡现象均显著减弱，提示Als3在SAA1的感知过程中发挥关键作用。此外，敲除白色念珠菌中ALS3的转录调控因子AHR1、BCR1与EFG1后，菌株对rhSAA1的细胞响应模式与als3/als3基因缺失突变体表现一致。全基因表达谱分析结果显示，rhSAA1可显著影响白色念珠菌细胞壁相关及代谢相关基因的表达。本研究揭示了rhSAA1抗白色念珠菌的活性，拓展了该蛋白的功能认知，也为理解感染过程中宿主与念珠菌的互作机制提供了新视角。本数据集包含经SAA1与磷酸盐缓冲液（Phosphate Buffered Saline, PBS）处理的白色念珠菌总RNA表达谱。