MOBILE DNA IN CANDIDA ALBICANS BIOLOGY AND EPIDEMIOLOGY

白色念珠菌是所有人类病原体中最普遍存在的， 引起皮肤和粘膜的感染， 个体和严重全身性疾病， 免疫力 正如C.白色念珠菌是各种各样的原因， 感染，它可以显示各种各样的形态和其他 表型 在C.白色念珠菌是由于高 遗传不稳定性的水平。 这种变异性可以通过 高频率的形态学变化，耐药性突变， 染色体畸变和重组转换系统。 的 本提案中的实验旨在确定分子 这种不稳定的基础。 该提案中的实验将：1）检查基因的运动 经历重组转换的家庭，2）确定机制 对于自发突变和形态变异，3）构建一个 念珠菌染色体的物理图谱，并使用它来评估的性质， 在自然界中看到的变异核型，和4）检查遗传的程度， 感染期间的变化。 将开发几种新技术用于念珠菌遗传学 系统 这些包括酿酒酵母穿梭人工 染色体载体和鉴定纯合位点的方法-- 念珠菌染色体的定向突变体。 聚合酶链式反应 (PCR)将开发用于检测C.组织中的白色念珠菌 样品 将努力整合在以下方面进行的遗传分析： 实验室菌株与自然变异，已被广泛 表征了 这些努力应该揭示哪些遗传机制 变异在感染周期中是重要的， 更重要的是， 特色

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.