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双组分反应调节因子Skn7属于调节白色念珠菌形态发生的转录因子网络,并独立限制形态发生诱导的活性氧积累。

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.

作者信息

Basso Virginia, Znaidi Sadri, Lagage Valentine, Cabral Vitor, Schoenherr Franziska, LeibundGut-Landmann Salomé, d'Enfert Christophe, Bachellier-Bassi Sophie

机构信息

Institut Pasteur, INRA, Unité Biologie et Pathogénicité Fongiques, 25 rue du Docteur Roux, Paris, France.

Univ. Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, rue du Dr. Roux, Paris, France.

出版信息

Mol Microbiol. 2017 Oct;106(1):157-182. doi: 10.1111/mmi.13758. Epub 2017 Aug 22.

Abstract

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.

摘要

Skn7是一种保守的真菌热休克因子型转录调节因子。它参与维持细胞壁完整性,并调节酿酒酵母中的渗透/氧化应激反应(OSR),在酿酒酵母中它是双组分信号转导系统的一部分。在此,我们全面研究了Skn7在人类真菌病原体白色念珠菌中的功能。我们提供的证据强化了功能差异,即失去了细胞壁/渗透应激保护作用,并获得了在固体培养基上调节形态发生的能力。通过全基因组表达和定位技术相结合来绘制Skn7转录调控网络,结果表明其具有涵盖OSR和丝状生长的双重调节作用。遗传相互作用分析揭示了Skn7与形态发生的主要调节因子之间存在密切的功能相互作用,这些调节因子包括Efg1、Cph1和Ume6。细胞内生化分析表明,在固体培养基上诱导菌丝形成的条件下,Skn7对于限制活性氧(ROS)的积累至关重要。有趣的是,使用定点诱变进行的功能域映射使得Skn7在形态发生中的功能与对细胞内ROS的保护作用得以分离。我们的研究确定Skn7是控制白色念珠菌丝状生长的转录调控网络的一个组成部分,并阐明了白色念珠菌在形态发育过程中如何依赖一种进化上保守的调节因子来保护自身免受细胞内ROS的影响。

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