S. Cerevisiae Emergence of an Opportunistic Pathogen

机会性病原体的酿酒酵母的出现

• 批准号: 7369742
• 负责人: John H. McCusker
• 金额: $ 25.22万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369742
• 关键词: Antifungal Therapy; Clinical; Complement; Complex; Development; Fungal Drug Resistance; Future; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Growth; Health; Hereditary Disease; High temperature of physical object; Human; Human body; In Vitro; Infection; Laboratories; Laboratory mice; Maps; Modeling; Mus; Nature; Pathogenesis; Pathogenicity; Pathway interactions; Phenotype; Population; Process; Proliferating; Quantitative Genetics; Quantitative Trait Loci; Relative (related person); Research Personnel; SNP genotyping; Saccharomyces cerevisiae; Site; Testing; Virulence; Virulent; base; fungus; genome sequencing; improved; in vivo; insight; killings; microbial; microorganism; pathogen; sugar; trait

The broad long term goals of this project are: 1.) To develop a detailed understanding of the emergence of S. cerevisiae as an opportunistic pathogen. 2.) To develop S. cerevisiae as a robust model to study the genetically complex phenotypes of pathogenicity and virulence. & 3.) To develop S. cerevisiae as a robust microbial model to study quantitative genetics. The specific aims of this project are: 1.) To determine the genetic basis for the very low in vivo survival-proliferation of the laboratory (S288c) strain and the very high in vivo survival-proliferation of the clinically derived (YJM145) strain S. cerevisiae genetic backgrounds. 2.) To determine the genetic basis for the difference between the non-lethal $288c and lethal YJM145 infection phenotypes. 3.) To examine a large S. cerevisiae population and determine the generality of virulence phenotypes and genotypes. The health relatedness of this project is twofold. First, the identification of the genes that differ between (i) low vs. high in vivo survival-proliferation and (ii) non-lethal vs. lethal strains ofS. cerevisiae is informative with respect to both the emergence of an opportunistic pathogen and what pathogen fungi require to survive-proliferate in and kill the host. Second, examination of the S. cerevisiae population will tell us the generality of virulence and virulence related phenotypes and genotypes. In both cases, we gain insight into the basics of fungal virulence that will aid in the development of antifungal therapies. Unfortunately the underlying basis of fungal pathogenesis is very poorly understood. Using S. cerevisiae, both in vivo survival-proliferation and lethal infections can be examined in ways that are not feasible in more common pathogenic fungi. Understanding the underlying basis of in vivo survival-proliferation and lethal infections aids our understanding of these processes in other pathogenic fungi. We will achieve these goals (i) by mapping the loci/identifying the genes responsible for the in vivo survival-proliferation phenotype and (ii) examining the larger S. cerevisiae population both phenotypically, for virulence and virulence-associated traits, and genotypically, for virulence-related genes.

这个项目的长期目标是：1.)对酿酒酵母作为一种机会性病原体的出现有一个详细的了解。2.)发展酿酒酵母作为研究致病和毒力遗传复杂表型的稳健模型。&3.)发展酿酒酵母作为研究数量遗传学的稳健微生物模型。 这个项目的具体目标是：1.)确定实验室菌株(S288c)体内存活-增殖极低和临床来源酿酒酵母(YJM145)菌株体内存活-增殖极高的遗传基础。2.)确定非致死性$288C和致死性YJM145感染表型差异的遗传基础。3.)检查大量的酿酒酵母种群，并确定毒力表型和基因类型的共性。 这个项目与健康有关有两个方面。首先，鉴定(I)低和高活体存活-增殖和(Ii)非致死性和致死性OFS株之间的差异基因。关于机会性病原体的出现以及病原体真菌生存所需的条件--在宿主体内增殖并杀死宿主，酿酒酵母提供了丰富的信息。其次，对酿酒酵母种群的检测将告诉我们毒力和与毒力相关的表型和基因类型的共性。在这两种情况下，我们都能深入了解真菌毒力的基本情况，这将有助于抗真菌疗法的发展。不幸的是，人们对真菌发病的潜在基础知之甚少。使用酿酒酵母，体内的存活-增殖和致命感染都可以用在更常见的致病真菌中不可行的方式进行检测。了解体内生存-增殖和致命感染的潜在基础有助于我们理解其他病原真菌的这些过程。我们将实现这些目标：(I)通过定位基因座/识别负责体内生存-增殖表型的基因，以及(Ii)检查较大的酿酒酵母群体，包括表型、毒力和毒力相关特征，以及基因型态，毒力相关基因。