MODELS OF CANDIDA ALBICANS--HOST INTERACTIONS

白色念珠菌是人类最重要的真菌病原体， 播散性念珠菌感染的发病率继续上升。这 真菌是遗传和分子方法难以解决的问题，因为它具有 二倍体状态和缺乏已知的性周期。尽管如此，具有 构建了影响毒力的目标基因的突变。 最近，这些菌株与一株临床分离的亲本菌株同源， 它们可以与之相比较。到目前为止，比较包括 固体和液体介质上生长特性的研究，以及 注射入动物体内，比较动物的存活率。 为了了解某些基因的突变是如何影响 念珠菌在宿主中传播的能力，细胞培养模型 念珠菌在传播过程中与之相互作用的三个关键组织将 被建立起来。肠上皮细胞株将被用来代表 粘膜屏障，巨噬细胞代表宿主吞噬细胞，以及 内皮细胞代表血管壁屏障。现有 假丝酵母突变株将用于建立这些细胞系作为模型 寄主-真菌相互作用系统。下一步将是确定 参与这种相互作用的念珠菌基因，通过建立 分离差异表达基因的程序。这些基因将 然后在假丝酵母菌中研究它们对宿主的影响-- 真菌的相互作用将在细胞培养模型中进行研究。

Candida albicans is the most important human fungal pathogen, and the incidence of disseminated candidal infection is continuing to rise. This fungus is intractable to genetic and molecular approaches due to its diploid state and lack of a known sexual cycle. Nevertheless, strains with mutations in targeted genes, which affect virulence, were constructed recently, These strains are isogeneic to a clinical isolate parent strain, with which they can be compared. So far, comparisons have consisted of studies of growth characteristics on solid and liquid media, as well as injection into animals and comparisons of animal survival. In order to understand how mutations in certain genes affect Candida's ability to disseminate in the host, cell culture models for three key tissues with which Candida interacts during dissemination will be established. Intestinal epithelial cell lines will be used to represent the mucosal barrier, macrophages to represent host phagocytes, and endothelial cells to represent the blood vessel wall barrier. Existing Candida mutant strains will be used to establish these cell lines as model systems of host-fungus interaction. The next step will be to identify Candida genes that are involved in this interaction, by established procedures for isolating differentially expressed genes. These genes will then be studied in Candida and the effect of their deletion of the host- fungus interaction will be studied in the cell culture models.