Discovery of a "white-gray-opaque" tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation.
Discovery of a "white-gray-opaque" tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation.
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白色念珠菌中“白-灰-不透明”三稳态表型转换系统的发现：非遗传多样性在宿主适应中的作用
DOI：
10.1371/journal.pbio.1001830
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发表时间：
2014-04
期刊：
影响因子：
9.8
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Tao L;Du H;Guan G;Dai Y;Nobile CJ;Liang W;Cao C;Zhang Q;Zhong J;Huang G
这项研究描述了人类真菌病原体白色念珠菌中一种新的“白-灰-不透明”三稳定表型转换系统，揭示了这种有机体适应不断变化的环境的能力的额外复杂性。非遗传表型变异在微生物对环境变化的适应中起着关键作用。白色念珠菌是一种主要的人类真菌病原体，可以在几种形态表型之间切换。这种能力对它的共生生活方式和引起感染的能力至关重要。在这里，我们报告了在白色念珠菌中发现的一种新的形态形式，称为“灰色”表型，它与先前报道的白色和不透明表型形成了一个三稳定的表型转换系统。白色、灰色和不透明的细胞类型在许多方面不同，包括细胞和菌落外观、交配能力、分泌的天冬氨酸蛋白酶（Sap）活性和毒力。在三种细胞类型中，灰色细胞表现出最高的Sap活性和最高的引起皮肤感染的能力。这三种表型形成了一个不依赖于交配型位点（MTL）调控的三稳态表型转换系统。灰色细胞的交配效率是白色细胞的1000多倍，但比不透明细胞的效率低。我们进一步证明了白-不透明转换的主调控因子Wor1对于不透明细胞的形成是必不可少的，但对于白-灰转换则不是必需的。Efg1调节因子对于维持白色表型是必需的，但对于灰色-不透明的过渡则不是必需的。有趣的是，wor1/wor1 efg1/efg1双突变体锁定在灰色表型中，这表明wor1和efg1可能协同起作用，并在灰色细胞形成的调控中发挥核心作用。全球转录分析表明，白色、灰色和不透明细胞表现出不同的基因表达谱，这在一定程度上解释了它们在引起感染、对不同宿主生态位的适应能力、代谢谱和应激反应方面的差异。因此，白色念珠菌的白-灰-不透明三稳态表型转换系统可能在这种常见的共生和致病真菌的广泛生物学方面发挥重要作用。白色念珠菌以多种细胞形式生长的能力——一种被称为表型可塑性的现象——对它的生存和它在人类宿主中茁壮成长并引起感染的能力至关重要。在这项研究中，我们报道了一种新的白色念珠菌，“灰色”表型，它可能增强适应性，并赋予这种重要的致病酵母在某些宿主环境中的适应性优势。灰色细胞类型，与之前发现的“白色”和“不透明”细胞类型一起，形成了一个三稳定的表型转换系统。这三种表型在细胞和集落外观、全球转录谱、分泌天冬氨酸蛋白酶（降解宿主组织和释放营养物质的酶）的产生以及不同感染模型中的毒力方面存在差异。此外，灰色细胞表现出的交配能力水平介于白色细胞和不透明细胞之间。我们进一步证明，两个关键的转录调控因子，Wor1和Efg1，在“白-灰-不透明”的可信赖转换的调控中发挥核心作用。我们的研究揭示了一个多稳定和可遗传的开关系统，表明采用不同的形态形式来响应环境变化可能比以前认为的要复杂得多。
This study describes a novel “white-gray-opaque” tristable phenotypic switching system in the human fungal pathogen Candida albicans, revealing additional complexity in this organism's ability to adapt to changing environments. Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the “gray” phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide range of biological aspects in this common commensal and pathogenic fungus. The capacity of the yeast Candida albicans to grow in several cellular forms—a phenomenon known as phenotypic plasticity—is critical for its survival and for its ability to thrive and cause infection in the human host. In this study, we report a novel form of C. albicans, the “gray” phenotype, which may enhance fitness and confer an adaptive advantage for this important pathogenic yeast in certain host environments. The gray cell type, together with the previously discovered “white” and “opaque” cell types, forms a tristable phenotypic switching system. The three phenotypes differ in their cellular and colony appearance, their global transcriptional profiles, their production of secreted aspartyl proteinases (enzymes that degrade host tissues and release nutrients), and their virulence in different infection models. Moreover, gray cells exhibit a level of mating competency that is intermediate between that of white and opaque cells. We further demonstrate that two key transcriptional regulators, Wor1 and Efg1, play central roles in the regulation of the “white-gray-opaque” tristable transitions. Our study reveals a multi-stable and heritable switching system, indicating that the adoption of distinct morphological forms in response to environmental change could be much more elaborate than previously thought.
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影响因子：
3.6
作者：
Hnisz D;Schwarzmüller T;Kuchler K
通讯作者：
Kuchler K
影响因子：
5.2
作者：
Huang G
通讯作者：
Huang G
DOI：
10.1073/pnas.0605270103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Huang, Guanghua;Wang, Huafeng;Liu, Haoping
通讯作者：
Liu, Haoping
DOI：
10.1099/00221287-136-10-1925
发表时间：
1990-10-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
BERGEN, MS;VOSS, E;SOLL, DR
通讯作者：
SOLL, DR
影响因子：
3.1
作者：
RAY, TL;PAYNE, CD
通讯作者：
PAYNE, CD