GENETIC VARIABILITY OF THE YEAST CANDIDA ALBICANS

白色念珠菌酵母的遗传变异

• 批准号: 6261155
• 负责人: Fred Sherman
• 金额: $ 23.69万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-03-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6261155
• 关键词: Candida albicans; DNA binding protein; Escherichia coli; binding sites; chromosome aberrations; computer assisted sequence analysis; fungal genetics; gene deletion mutation; gene expression; gene frequency; gene interaction; gene mutation; genetic library; genetic polymorphism; genetic promoter element; genetic regulation; genetic strain; genetic transcription; karyotype; microarray technology; mutant; phenotype; protein binding; structural genes; yeast two hybrid system

DESCRIPTION (Verbatim from Applicant's Abstract): Clinical isolates of the pathogenic yeast Candida albicans exhibit extensive variation in electrophoretic karyotypes and in phenotypic polymorphism. In this connection, systematic studies conducted in our laboratory revealed that laboratory strains of C. albicans spontaneously give rise to high frequencies of many different types of mutants having altered phenotypes and karyotypes. The significance of the chromosomal alterations was established with spontaneous mutants that acquired the ability to utilize alternative carbon sources. A causal relationship was established with a series of Sou- to Sou+ to Sou- to Sou+ derivatives, in which the Sou- (L-sorbose none-utilizing) and Sou+ (L-sorbose utilizing) strains were, respectively, disomic and monosomic for chromosome 5. Furthermore, transcription of the SOU1 gene, required for L-sorbose utilization, was regulated by the copy number of chromosome 5, in spite of the fact that SOU1 resides on a different chromosome. A hypothetical negative regulator, CSU51, was postulated to reside on chromosome 5, such that transcription of SOU1 is dependent on the ratio of the CSU51 to SOU1 copy number. Other examples of negative regulation by chromosome copy number include the utilization of D-arabinose, Aru- to Aru+, and resistance to the antifungal agent, fluconazole, FluS to FluR, thus establishing a general regulatory mechanism. The major long-term goal of the proposed research is to determine mechanisms of this newly-discovered regulatory process in C. albicans, by which gene expression is controlled by chromosome copy number. Several candidates of the negative regulator residing on chromosome 5 have been isolated from a library of chromosome 5 DNA, and these are being characterized. These regulators will be investigated for their direct or indirect interaction with the SOU1 structural gene. The additional negative regulators, which were retrieved from a total genomic library, and which are located on different chromosomes, will be analyzed for their involvement in the regulatory network controlled by chromosome copy number. This work establishes for the first time a negative regulatory network for a secondary carbon source in an important pathogen.

描述（来自申请人摘要的逐字描述）： 致病性酵母菌白色念珠菌在 电泳核型和表型多态性。在这方面， 我们实验室进行的系统研究显示，实验室菌株 梭白色念珠菌自发地引起高频率的许多不同的 具有改变的表型和核型的突变体类型。的意义 染色体改变是用自发突变体建立的， 获得了利用替代碳源的能力。的因果 建立了一系列的苏-苏+苏-苏+ 衍生物，其中Sou-（L-山梨糖非利用）和Sou+（L-山梨糖 利用）菌株分别为5号染色体的二体和单体。 此外，L-山梨糖所需的SOU 1基因的转录 利用，是由5号染色体的拷贝数，尽管 SOU 1位于不同的染色体上。假设的否定 调节子CSU 51被假定位于5号染色体上， SOU 1的转录取决于CSU 51与SOU 1拷贝的比例 number.染色体拷贝数负调控的其他例子包括 D-阿拉伯糖的利用率、Aru-对Aru+的利用率和抗真菌药物的耐药性 代理，氟康唑，FluS到FluR，从而建立了一个通用的监管 机制拟议研究的主要长期目标是确定 这一新发现的调节过程在C.白色念珠菌， 基因表达受染色体拷贝数控制。几个候选人 存在于5号染色体上的负调节因子已经从 5号染色体DNA文库，这些正在被表征。这些 监管机构将调查其直接或间接的相互作用， SOU 1结构基因额外的负调节因子， 从总基因组文库中检索，并且其位于不同的 染色体，将分析它们在调控网络中的参与 由染色体拷贝数控制。这项工作首次建立了 一个负调控网络的第二碳源在一个重要的 病原体