S. Cerevisiae Emergence of an Opportunistic Pathogen

机会性病原体的酿酒酵母的出现

• 批准号: 7185090
• 负责人: John H. McCusker
• 金额: $ 31.02万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185090
• 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.

该项目的长期目标是：（1）对S.酿酒酵母作为机会致病菌。2.）的情况。发展S.酿酒酵母作为一个强大的模型，研究遗传复杂的表型的致病性和毒力。和3.）发展S.酿酒酵母作为一个强大的微生物模型，研究数量遗传学。 该项目的具体目标是：（1）。为确定实验室菌株（S288 c）极低的体内存活-增殖和临床衍生菌株（YJM 145）极高的体内存活-增殖的遗传基础。酿酒酵母的遗传背景。2.）的情况。确定非致死性$288c和致死性YJM 145感染表型之间差异的遗传基础。3.）第三章检查一个大的S。酿酒酵母群体，并确定毒力表型和基因型的一般性。 该项目的健康相关性是双重的。首先，鉴定在（i）低与高体内存活-增殖和（ii）非致死与致死S.酿酒酵母菌提供关于机会致病菌的出现和致病真菌需要什么来在宿主中存活-增殖和杀死宿主的信息。第二，对S.酿酒酵母群体的毒性和毒性相关的表型和基因型的一般性。在这两种情况下，我们深入了解真菌毒力的基础知识，这将有助于抗真菌治疗的发展。不幸的是，对真菌发病机理的基础了解甚少。利用S.酿酒酵母，无论是在体内存活增殖和致死感染可以检查的方式，是不可行的，在更常见的病原真菌。了解体内存活增殖和致死性感染的潜在基础有助于我们了解其他病原真菌中的这些过程。我们将实现这些目标（i）通过定位基因座/鉴定负责体内存活-增殖表型的基因和（ii）检查较大的S。酿酒酵母群体的毒力和毒性相关性状在表型上，以及毒性相关基因在基因型上。