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Developmental biology of Candida albicans and Candida glabrata and its clinical significance.

机译:白色念珠菌和光滑念珠菌的发育生物学及其临床意义。

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摘要

Candida albicans and Candida glabrata are yeast pathogens that infect humans. The research reported here deals primarily with phenotypic switching in these two organisms. First, to identify the locus that controls white-opaque switching, a reverse genetics strategy was used in which the promoter of a phase-regulated trans-acting factor gene, EFG1, was functionally characterized. It is demonstrated that regulation involves overlapping promoters that control white and opaque phase-specific transcripts, and that a white phase-specific protein complex interacts with a white phase-specific activation region. This work represents the first step in this reverse genetics strategy. Second, experiments were performed to identify the site of C. albicans mating in the human body, since mating has recently been demonstrated to depend on switching. Using a mouse cutaneous model, it is demonstrated that skin facilitates mating. Third, it is demonstrated for the first time that C. glabrata possesses two phenotypic switching systems, the core switching system, in which cells switch between four phenotypes differing in the intensity of brown colony coloration on CuSO4-containing agar, and the irregular wrinkle switching system in which cells switch between smooth or an irregular wrinkle phenotype containing predominantly pseudohyphal cells. Core switching regulates the expression of the genes MT-II and HLP, and the mating type gene MTLalpha1, in a graded manner. Fourth, an analysis of isolates from patients suffering from vaginal C. glabrata infections reveal that both phenotypic switching and mating type switching occur in the host, that switch phenotypes selectively colonize specific anatomical locations, and that both a and alpha strains cause infection.
机译:白色念珠菌和光滑念珠菌是感染人类的​​酵母菌病原体。此处报道的研究主要涉及这两种生物的表型转换。首先,为了确定控制白不透明转换的基因座,采用了反向遗传学策略,在该策略中,对功能性相调控的反式作用因子基因EFG1的启动子进行了表征。证明调节涉及重叠的启动子,其控制白色和不透明的阶段特异性转录本,并且白色阶段特异性蛋白复合物与白色阶段特异性激活区相互作用。这项工作代表了这种反向遗传学策略的第一步。第二,进行实验以鉴定白色念珠菌在人体内的交配部位,因为最近已证明交配依赖于开关。使用小鼠皮肤模型,证明皮肤促进交配。第三,首次证明了光滑念珠菌具有两个表型转换系统,即核心转换系统,其中细胞在含CuSO4的琼脂上棕色集落着色强度不同的四种表型之间进行切换,以及不规则的皱纹切换细胞在光滑或不规则的皱纹表型之间切换的系统,主要包含假菌丝细胞。核心转换以分级方式调节基因MT-II和HLP以及交配型基因MTLalpha1的表达。第四,对来自患有光滑念珠菌阴道感染的患者的分离株的分析表明,表型转换和交配类型转换均在宿主中发生,转换表型选择性地定植在特定的解剖位置,并且α和α菌株均引起感染。

著录项

  • 作者

    Lachke, Salil Anil.;

  • 作者单位

    The University of Iowa.;

  • 授予单位 The University of Iowa.;
  • 学科 Biology Microbiology.;Biology Molecular.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 337 p.
  • 总页数 337
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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