MOBILE DNA IN CANDIDA ALBICANS BIOLOGY AND EPIDEMIOLOGY

白色念珠菌是人类最普遍的病原体之一， 在其他健康的人中引起皮肤和粘膜的感染 个体和严重系统性疾病受损的个体 豁免权。就像白色念珠菌是引起各种各样的 感染，它可以表现出各种各样的形态和其他 表型。白色念珠菌的变异性很大程度上是由于 遗传不稳定的程度。这种可变性可以通过以下方式检测到 高频率的形态变化，耐药突变， 染色体畸变和重组开关系统。这个 这个方案中的实验是为了确定分子 这是这种不稳定的基础。 该提案中的实验将：1)检查基因的运动 经历重组转换的家族，2)确定机制 对于自发突变和形态变异，3)构建一个 假丝酵母菌染色体的物理图谱并用它来评估 自然界中可见的变异核型，以及4)检查遗传的程度 感染过程中的变异。 几项新技术将被开发用于假丝酵母菌的遗传 系统。其中包括假丝酵母菌人工穿梭 染色体载体和鉴定纯合子位点的程序-- 念珠菌染色体的定向突变体。聚合酶链式反应 将建立检测组织中白色念珠菌的聚合酶链式反应方法 样本。 将努力整合已完成的遗传分析 带有天然变异的实验室菌株已经被广泛 特色化的。这些努力应该揭示出基因的哪些机制 变异在感染周期中是显著的，而其他 更重要的是出现了毒力变化的新毒株 特点。

Candida albicans is among the most ubiquitous of all human pathogens, causing infections of the skin and mucosa in otherwise healthy individuals and severe systemic disease in individuals with impaired immunity. Just as C. albicans is the cause of a wide variety of infections, it can display a great variety of morphologies and other phenotypes. Much of the variability seen with C. albicans is due to high levels of genetic instability. This variability can be detected through high frequencies of morphologic changes, mutation to drug resistance, chromosome aberrations, and recombinational switching systems. The experiments in this proposal are designed to determine the molecular basis of this instability. Experiments in the proposal will: 1) examine the movement of a gene family that undergoes recombinational switching, 2) determine mechanisms for spontaneous mutation and morphologic variation, 3) construct a physical map of a Candida chromosome and use it to assess the nature of variant karyotypes seen in nature, and 4) examine the extent of genetic variation during infection. Several new techniques will be developed for the Candida genetic system. These include Candida-Saccharomyces shuttle artificial chromosome vectors and procedures for identifying homozygous site-- directed mutants of the Candida chromosomes. A polymerase chain reaction (PCR) assay will be developed for the detection of C. albicans in tissue samples. Efforts will be made to integrate the genetic analyses done on laboratory strains with natural variants that have been extensively characterized. These efforts should reveal which mechanisms for genetic variation are significant in the infection cycle and others which are more important for the emergence of new strains with altered virulence characteristics.