Role of Transcription Factor CaNdt80p in Cell Separation, Hyphal Growth, and Virulence in Candida albicans
Role of Transcription Factor CaNdt80p in Cell Separation, Hyphal Growth, and Virulence in Candida albicans
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DOI：
10.1128/ec.00325-09
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发表时间：
2010-04-01
期刊：
影响因子：
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通讯作者：
Nantel, Andre
中科院分区：
文献类型：
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作者：
Sellam, Adnane;Askew, Christopher;Nantel, Andre
NDT 80/PhoG转录因子家族包括ScNdt 80 p，其是酿酒酵母中减数分裂进程的关键调节剂。在白色念珠菌中，该家族的成员CaNdt 80 p通过控制麦角固醇生物合成基因的表达来调节唑敏感性。我们以前证明，CaNdt 80 p启动子的目标，除了ERG基因，显着丰富的菌丝生长相关的基因。在这里，我们报告说，CaNdt 80 p确实需要菌丝生长在不同的诱导因子和适当表达的基因特征的丝状转录程序。这些包括编码细胞壁组分的值得注意的基因，如HWP 1，ECE 1，RBT 4和ALS 3。我们还表明，CaNdt 80 p是必不可少的完成细胞分离，通过直接转录调控的基因编码的几丁质酶Cht 3 p和细胞壁葡糖苷酶Sun 41 p。与它们的菌丝缺陷一致，在系统性念珠菌病的小鼠模型中，E180突变体是无毒的。有趣的是，基于功能结构域组织，CaNdt 80 p似乎是一个独特的调节器，其特征在于真菌亚门内的CTG分支。因此，本研究揭示了真菌NDT 80转录因子家族的新成员作为细胞分离，菌丝生长和毒力的调节剂的新作用。
The NDT80/PhoG transcription factor family includes ScNdt80p, a key modulator of the progression of meiotic division in Saccharomyces cerevisiae. In Candida albicans, a member of this family, CaNdt80p, modulates azole sensitivity by controlling the expression of ergosterol biosynthesis genes. We previously demonstrated that CaNdt80p promoter targets, in addition to ERG genes, were significantly enriched in genes related to hyphal growth. Here, we report that CaNdt80p is indeed required for hyphal growth in response to different filament-inducing cues and for the proper expression of genes characterizing the filamentous transcriptional program. These include noteworthy genes encoding cell wall components, such as HWP1, ECE1, RBT4, and ALS3. We also show that CaNdt80p is essential for the completion of cell separation through the direct transcriptional regulation of genes encoding the chitinase Cht3p and the cell wall glucosidase Sun41p. Consistent with their hyphal defect, ndt80 mutants are avirulent in a mouse model of systemic candidiasis. Interestingly, based on functional-domain organization, CaNdt80p seems to be a unique regulator characterizing fungi from the CTG clade within the subphylum Saccharomycotina. Therefore, this study revealed a new role of the novel member of the fungal NDT80 transcription factor family as a regulator of cell separation, hyphal growth, and virulence.