GENETIC VARIATION IN FUNGAL LUNG PATHOGENS AND HOSTS

肺部真菌病原体和宿主的遗传变异

• 批准号: 2519572
• 负责人: JOHN W. TAYLOR
• 金额: $ 20.97万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519572
• 关键词: AIDS; Coccidioides immitis; Filipino; North America; coccidioidomycosis; fungal genetics; genetic polymorphism; histoplasmosis; host organism interaction; human genetic material tag; human population genetics; human subject; major histocompatibility complex; microorganism culture; microorganism population study; microorganism reproduction; opportunistic infections; polymerase chain reaction; single strand conformation polymorphism

This proposal aims to apply comparative biology to the study of molecular genetic variation in diseases, caused by two fungal lung pathogens Coccidioides immitis and Histoplasma capsulatum, that pose severe clinical problem for HIV+ patients. This study is strongly influenced by reports last year of obtaining genes responsible for fungal disease and host resistance in plant systems. In these studies, prior knowledge of fungal genetic variation and host genetic variation were essential to success. In the long term, we hope that our data on pathogen and host genetic variation will make it attractive for medical mycologists to adopt the approaches developed by plant pathologists. Fungi. The part of this proposal devoted to fungi is made possible by our development of new methods to precisely define and analyze microbial nucleotide polymorphism. It is made timely by our discovery that Coccidioides immitis, long thought to be asexual, is recombining like a sexual organism in nature, and our demonstration that His to plasma capsulatum (already known to reproduce sexually in the lab) is likewise recombining in nature. The aims of this proposal are to: I) develop mating in C. immitis in the laboratory, 2) analyze genetic variation in C. immitis and H. capsulatum throughout North America, and 3) analyze genetic variation in C. immitis and H. capsulatum isolates taken from AIDS patients, from ethnic minorities known to be more susceptible to disseminated coccidioidomycosis, and from the environment. Host. The part of this proposal devoted to host genetic variation is made possible by advances in molecular characterization of the complex HLA locus in humans, and the observation that certain ethnic groups are an order-of-magnitude more likely to suffer disseminated coccidioidomycosis. The aim is to analyze HLA loci in Filipinos with disseminated coccidioidomycosis and compare these data with 500 haplotypes already determined for individuals in this ethnic group. Identification. Because we have new data for both fungi showing that isolates from different geographic locations are genetically isolated, we can design molecular identification systems to infer the geographic origin of clinical isolates. This information should be important to analyzing possible disease reactivation following HIV infection.

该建议旨在将比较生物学应用于分子研究 由两种真菌肺病原体引起的疾病遗传变异 球虫毒剂侵入炎和组织囊肿囊膜，造成严重的 HIV+患者的临床问题。这项研究受到强烈的影响 去年获得了负责真菌疾病的基因的报告和 植物系统中的宿主阻力。在这些研究中，先验知识 真菌遗传变异和宿主遗传变异对于 成功。从长远来看，我们希望我们的病原体和宿主数据 遗传变异将使医学真菌学家有吸引力 采用植物病理学家开发的方法。 真菌。我们的提案的一部分由我们的 开发精确定义和分析微生物的新方法 核苷酸多态性。我们发现的及时使 长期认为是无性恋的球球菌Immitis，像 自然界中的性生物以及我们的表现为等离子体 同样 重组自然。该提议的目的是：i）发展 实验室中的C. Immitis交配，2）分析遗传变异 C.流经炎和H.囊膜整个北美，3）分析 从遗传性炎和囊囊分离菌中的遗传变异 艾滋病患者，来自已知少数民族更容易受到影响的艾滋病患者 传播球菌菌症和环境。 主持人。该提案的一部分用于寄主遗传变异 通过复合HLA的分子表征的进步可能 人类中的基因座，以及某些种族是一个观察 降低阶级的可能性更有可能遭受散布的球菌病。 目的是分析菲律宾人的HLA基因座 球虫菌病并将这些数据与500个单倍型进行比较 为这个族裔中的个人确定。 鉴别。因为我们有两种真菌的新数据表明 来自不同地理位置的分离株是遗传分离的， 我们可以设计分子识别系统来推断地理 临床分离株的起源。这些信息对于 分析HIV感染后可能的疾病重新激活。