GENETIC VARIABILITY OF THE YEAST CANDIDA ALBICANS

描述（逐字摘自申请人摘要）：临床分离株 致病性酵母白色念珠菌表现出广泛的变异 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表明，实验室菌株 白色念珠菌自发地产生许多不同的高频率 具有改变的表型和核型的突变体类型。意义 染色体改变是通过自发突变体建立的 获得了利用替代碳源的能力。一个因果关系 通过一系列的 Sou- to Sou to Sou- to Sou 建立了关系 衍生物，其中 Sou-（L-山梨糖非利用性）和 Sou（L-山梨糖 利用）菌株的 5 号染色体分别为二体和单体。 此外，L-山梨糖所需的 SOU1 基因的转录 利用，受到 5 号染色体拷贝数的调节，尽管 事实上，SOU1 位于不同的染色体上。假设的否定 调节因子 CSU51 被假定位于 5 号染色体上，因此 SOU1 的转录取决于 CSU51 与 SOU1 拷贝的比例 数量。染色体拷贝数负调控的其他例子包括 D-阿拉伯糖、Aru-to Aru 的利用以及抗真菌药物的耐药性 剂，氟康唑，FluS 至 FluR，从而建立了通用监管 机制。拟议研究的主要长期目标是确定 白色念珠菌中这种新发现的调节过程的机制，通过该机制 基因表达受染色体拷贝数控制。几位候选人 位于 5 号染色体上的负调节因子已从 5 号染色体 DNA 文库，并且正在对其进行表征。这些 监管机构将因其直接或间接的互动而受到调查 SOU1结构基因。额外的负调节因子是 从总基因组库中检索，并且位于不同的位置 染色体，将分析它们参与调控网络的情况 由染色体拷贝数控制。本作品首次确立 重要的二次碳源负调控网络 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.