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A Versatile Overexpression Strategy in the Pathogenic Yeast Candida albicans: Identification of Regulators of Morphogenesis and Fitness

机译:一个多才多艺的表达策略在致病酵母白色念珠菌:形态和健身的监管机构的鉴定

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摘要

Candida albicans is the most frequently encountered human fungal pathogen, causing both superficial infections and life-threatening systemic diseases. Functional genomic studies performed in this organism have mainly used knock-out mutants and extensive collections of overexpression mutants are still lacking. Here, we report the development of a first generation C. albicans ORFeome, the improvement of overexpression systems and the construction of two new libraries of C. albicans strains overexpressing genes for components of signaling networks, in particular protein kinases, protein phosphatases and transcription factors. As a proof of concept, we screened these collections for genes whose overexpression impacts morphogenesis or growth rates in C. albicans. Our screens identified genes previously described for their role in these biological processes, demonstrating the functionality of our strategy, as well as genes that have not been previously associated to these processes. This article emphasizes the potential of systematic overexpression strategies to improve our knowledge of regulatory networks in C. albicans. The C. albicans plasmid and strain collections described here are available at the Fungal Genetics Stock Center. Their extension to a genome-wide scale will represent important resources for the C. albicans community.
机译:白色念珠菌是最常见的人类真菌病原体,既引起浅表感染又威胁着生命的全身性疾病。在这种生物中进行的功能基因组研究主要使用敲除突变体,并且仍然缺乏大量的过表达突变体。在这里,我们报告第一代白色念珠菌ORFeome的开发,过表达系统的改进以及两个新的白色念珠菌菌株新表达库的构建,这些基因过量表达信号网络的组成部分,特别是蛋白激酶,蛋白磷酸酶和转录因子。作为概念验证,我们筛选了这些集合中过表达会影响白色念珠菌的形态发生或生长速率的基因。我们的筛查结果鉴定了先前描述的基因在这些生物过程中的作用,证明了我们策略的功能以及以前与这些过程无关的基因。本文强调系统的过表达策略的潜力,以提高我们对白色念珠菌监管网络的了解。此处描述的白色念珠菌质粒和菌株集合可在真菌遗传学储备中心获得。它们扩展到全基因组规模将代表白色念珠菌社区的重要资源。

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