MODELS OF CANDIDA ALBICANS--HOST INTERACTIONS

白色念珠菌是最重要的人类真菌病原体， 播散性念珠菌感染的发病率继续上升。这 真菌是难以对付的遗传和分子方法，由于其 二倍体状态和缺乏已知的性周期。尽管如此， 构建了影响毒力的靶基因突变， 最近，这些菌株与临床分离的亲本菌株是同源的， 可以与之比较。到目前为止，比较包括 研究固体和液体培养基上的生长特性，以及 注射到动物中并比较动物存活率。 为了了解某些基因的突变如何影响 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相互作用的三个关键组织将 建立。肠上皮细胞系将用于代表 粘膜屏障，巨噬细胞代表宿主吞噬细胞，和 内皮细胞代表血管壁屏障。现有 念珠菌突变株将用于建立这些细胞系作为模型 宿主-真菌相互作用的系统。下一步将确定 通过建立参与这种相互作用的念珠菌基因， 分离差异表达基因的方法。这些基因将 然后在假丝酵母中进行研究，并研究其缺失宿主的影响- 将在细胞培养模型中研究真菌相互作用。

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.