Genome-wide association analysis of clinical vs. nonclinical origin provides insights into Saccharomyces cerevisiae pathogenesis.
Genome-wide association analysis of clinical vs. nonclinical origin provides insights into Saccharomyces cerevisiae pathogenesis.
复制标题
临床与非临床起源的全基因组关联分析提供了对酿酒酵母发病机理的见解。
DOI：
10.1111/j.1365-294x.2011.05225.x
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发表时间：
2011-10
影响因子：
4.9
通讯作者：
McCusker JH
中科院分区：
文献类型：
--
作者：
Muller LA;Lucas JE;Georgianna DR;McCusker JH
由于驯化的酿酒酵母菌株几个世纪以来一直被用于生产发酵食品和饮料，而没有明显的健康影响，酿酒酵母一直被认为是公认的安全(GRAS)微生物。然而，在人类群体中报告的粘膜和系统性酿酒酵母感染的数量有所增加，即使在相对健康的人中也发生了致命的感染。为了深入了解酿酒酵母的发病机制，提高我们对真菌病原体产生的认识，我们对酿酒酵母的临床来源和非临床来源进行了基于群体的全基因组环境关联分析。通过对44株临床菌株和44株来自不同地理来源和来源底物的非临床酿酒酵母菌株的高密度基因分型，我们确定了几个与临床背景相关的遗传位点。在VRP1、KIC1、SBE22和PDR5编码序列以及YGR146C的5‘上游区域的相关多态性表明伪菌丝的形成、细胞壁的强健维持和细胞的解毒在酿酒酵母致病中的重要性，并为后续验证酿酒酵母的毒力和毒力相关因素奠定了良好的基础。
Because domesticated Saccharomyces cerevisiae strains have been used to produce fermented food and beverages for centuries without apparent health implications, S. cerevisiae has always been considered a Generally Recognized As Safe (GRAS) microorganism. However, the number of reported mucosal and systemic S. cerevisiae infections in the human population has increased and fatal infections have occured even in relatively healthy individuals. In order to gain insight into the pathogenesis of S. cerevisiae and improve our understanding of the emergence of fungal pathogens, we performed a population-based genome-wide environmental association analysis of clinical versus non-clinical origin in S. cerevisiae. Using tiling array-based, high density genotypes of 44 clinical and 44 non-clinical S. cerevisiae strains from diverse geographical origins and source substrates, we identified several genetic loci associated with clinical background in S. cerevisiae. Associated polymorphisms within the coding sequences of VRP1, KIC1, SBE22 and PDR5, and the 5′ upstream region of YGR146C indicate the importance of pseudohyphal formation, robust cell wall maintenance and cellular detoxification for S. cerevisiae pathogenesis, and constitute good candidates for follow-up verification of virulence and virulence-related factors underlying the pathogenicity of S. cerevisiae.