The zinc cluster transcription factor Czf1 regulates cell wall architecture and integrity in Candida albicans
The zinc cluster transcription factor Czf1 regulates cell wall architecture and integrity in Candida albicans
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DOI：
10.1111/mmi.14727
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发表时间：
2021-05-11
影响因子：
3.6
通讯作者：
Morschhaeuser, Joachim
中科院分区：
文献类型：
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作者：
Mottola, Austin;Ramirez-Zavala, Bernardo;Morschhaeuser, Joachim
真菌细胞壁对于维持细胞的完整性和调节细胞与环境的相互作用是必不可少的。它是一种高度灵活的细胞器，其组成和组织可以根据不断变化的生长条件进行调整。在致病酵母白色念珠菌中，一个信号通路网络调节细胞壁的结构，而这些通路中存在缺陷的突变株对细胞壁压力高度敏感。通过利用所有白念珠菌锌簇转录因子的基因激活形式的文库，我们发现高活性的JCHF1挽救了不同蛋白激酶缺失突变体对细胞壁应激的超敏反应。高活性的JCHF1诱导了许多具有细胞壁相关功能的基因的表达，并导致细胞壁结构的明显变化。白念珠菌czf1 Delta突变株对抑制细胞壁生物合成的抗真菌药物卡泊芬净过敏。细胞壁结构的改变是由于细胞过度活跃或缺乏JCHF1导致的，导致中性粒细胞对白色念珠菌的识别增加。我们的结果表明，作为丝状生长和白色不透明切换的调节者，JCHF1控制着细胞壁基因的表达，并调节细胞壁的结构。
The fungal cell wall is essential for the maintenance of cellular integrity and mediates interactions of the cells with the environment. It is a highly flexible organelle whose composition and organization is modulated in response to changing growth conditions. In the pathogenic yeast Candida albicans, a network of signaling pathways regulates the structure of the cell wall, and mutants with defects in these pathways are hypersensitive to cell wall stress. By harnessing a library of genetically activated forms of all C. albicans zinc cluster transcription factors, we found that a hyperactive Czf1 rescued the hypersensitivity to cell wall stress of different protein kinase deletion mutants. The hyperactive Czf1 induced the expression of many genes with cell wall-related functions and caused visible changes in the cell wall structure. C. albicans czf1 Delta mutants were hypersensitive to the antifungal drug caspofungin, which inhibits cell wall biosynthesis. The changes in cell wall architecture caused by hyperactivity or absence of Czf1 resulted in an increased recognition of C. albicans by human neutrophils. Our results show that Czf1, which is known as a regulator of filamentous growth and white-opaque switching, controls the expression of cell wall genes and modulates the architecture of the cell wall.