Kastora Stavroula L, Herrero-de-Dios Carmen, Avelar Gabriela M, Munro Carol A, Brown Alistair J P
Aberdeen Fungal Group, MRC Centre for Medical Mycology, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Mol Microbiol. 2017 Aug;105(4):620-636. doi: 10.1111/mmi.13722. Epub 2017 Jun 19.
The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host-imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these 'non-standard' growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source-conditional manner. SFP1 is induced in stressed glucose-grown cells, whereas RTG3 is upregulated in stressed lactate-grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source-dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation.
临床上重要的酵母白色念珠菌的致病性取决于对宿主施加的应激的强烈反应。这些应激反应通常是在30°C的体外人工生长培养基上进行剖析的，这些培养基并不能模拟宿主生态位。然而，已知宿主输入，如碳源或温度的变化，会影响白色念珠菌的应激适应。因此，我们进行了筛选，以确定在生理相关的羧酸上生长和在高温下生长时促进抗应激的新型调节因子。这些筛选表明，在这些“非标准”生长条件下，除了经典的Hog1、Cap1和Cta4应激途径外，还需要许多未表征的调节因子来实现抗应激。特别是，两个转录因子（Sfp1和Rtg3）以相互的、碳源条件依赖的方式促进抗应激。SFP1在应激的葡萄糖生长细胞中被诱导，而RTG3在应激的乳酸生长细胞中上调。Rtg3和Sfp1以碳源依赖的方式调节关键应激基因如CTA4、CAP1和HOG1的表达。这些机制是白色念珠菌sfp1细胞在葡萄糖上生长以及rtg3细胞在乳酸上生长时应激敏感性的基础。数据表明，白色念珠菌利用环境条件依赖的调节机制在宿主定殖过程中保持抗应激能力。
