GENETIC VARIABILITY OF THE YEAST CANDIDA ALBICANS

描述(逐字摘自申请人摘要)：临床分离株 致病酵母白色念珠菌表现出广泛的变异 电泳法核型分析和表型多态性分析。在这方面， 在我们实验室进行的系统研究表明，实验室菌株 白念珠菌自发性地引起许多不同的高频 具有改变表型和核型的突变体类型。的重要意义。 染色体的改变是通过自发突变建立起来的 获得了利用替代碳源的能力。因果关系 通过一系列的Sou-to Sou to Sou-to Sou建立了关系 衍生产品，其中Sou-(L-山梨糖未利用)和Sou(L-山梨糖) 利用)菌株分别为5号染色体二体和单体。 此外，L-山梨糖所需的SOU1基因的转录 利用，由5号染色体的拷贝数调节，尽管 SOU1位于不同的染色体上。假设性的否定 据推测，调节子CSU51位于5号染色体上，因此 SOU1的转录依赖于CSU51与SOU1拷贝的比率 数。其他由染色体拷贝数负调控的例子包括 D-阿拉伯糖、Aru-to Aru的利用及其对真菌的抗性 药剂、氟康唑、氟尿嘧啶，从而建立了通用的调控机制 机制。拟议研究的主要长期目标是确定 这一新发现的白色念珠菌调控过程的机制，通过 基因的表达受染色体拷贝数的控制。几位候选人 位于5号染色体上的负调控子是从一种 5号染色体DNA文库，这些正在被鉴定。这些 监管机构将因直接或间接与 SOU1结构基因。额外的负向调节器，它们是 从总基因组文库中检索，并且位于不同的 染色体，将分析它们参与调控网络的情况 受染色体拷贝数控制。这项工作是第一次建立 在一个重要的次要碳源中，负向监管网络 病原体。

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.