The two-component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis-induced ROS accumulation
The two-component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis-induced ROS accumulation
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DOI：
10.1111/mmi.13758
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发表时间：
2017-10-01
影响因子：
3.6
通讯作者：
Bachellier-Bassi, Sophie
中科院分区：
文献类型：
--
作者：
Basso, Virginia;Znaidi, Sadri;Bachellier-Bassi, Sophie
Skn 7是一种保守的真菌热休克因子型转录调节因子。它参与维持细胞壁的完整性，并调节渗透/氧化应激反应（OSR）在S。酿酒酵母，其中它是双组分信号转导系统的一部分。在这里，我们全面解决Skn 7在人类真菌病原体白色念珠菌中的功能。我们提供的证据加强功能的分歧，与细胞壁/渗透压保护作用的损失和收购的能力，以调节固体培养基上的形态发生。通过全基因组表达和定位技术相结合，绘制Skn 7转录电路图，指出了OSR和丝状生长的双重调节作用。遗传相互作用分析揭示了Skn 7和形态发生的主调节因子（包括Efg 1、Cph 1和Ume 6）之间的密切功能相互作用。细胞内生化分析表明，Skn 7是至关重要的限制积累的活性氧（ROS）在固体培养基上的诱导条件下。有趣的是，使用定点诱变的功能结构域定位允许Skn 7在形态发生中的功能与对细胞内ROS的保护脱钩。我们的工作确定Skn 7作为控制C. albicans丝状生长，并阐明了C.白色念珠菌依赖于一种进化上保守的调节因子来保护自身在形态发育过程中免受细胞内ROS的影响。
Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) in filament-inducing conditions on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.