NICHE SPECIFIC PATHOBIOLOGY OF CANDIDA ALBICANS

白色念珠菌的特定病理学

• 批准号: 6532800
• 负责人: William A. Fonzi
• 金额: $ 24万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532800
• 关键词: Candida albicans; DNA binding protein; DNA footprinting; biological polymorphism; fungal genetics; gel mobility shift assay; gene expression; genetic regulation; green fluorescent proteins; host organism interaction; immunofluorescence technique; membrane proteins; molecular cloning; molecular pathology; protein protein interaction; protein structure function; regulatory gene; transcription factor; virulence

DESCRIPTION: (Adapted from Applicant's Abstract) Candida albicans is an opportunistic pathogen of AIDS patients. These individuals typically develop oral and esophageal infections due to this fungus. More recently, candidemia has been recognized as a nosocomial complication in AIDS patients with significant associated mortality. Long-term and prophylactic antifungal treatment of AIDS patients has resulted in the emergence of clinically resistant C. albicans strains. This situation is exacerbated by the limited arsenal of efficacious drugs. Much of the biology of C. albicans is unknown due, in part, to the past difficulties in the genetic manipulation of this fungus. However, a substantial amount of data implicate the dimorphic ability of C. albicans in the development of disease. In the case of C. albicans, dimorphism refers to the ability of this organism to adopt either a yeast (single-celled) or hyphal (multicellular filamentous) morphology. The relatively recent development of methods to overcome many of the technical problems in the genetic dissection of C. albicans now permits a closer mechanistic examination of the role of dimorphism in disease. The aim of the present proposal is the investigation of a particular genetic determinant of dimorphism in C. albicans, the gene HWP1. HWP1 was isolated in a screen for genes expressed only in the filamentous form. HWP1 is required for filamentation and virulence in a mouse model of systemic disease, but is not required for gastrointestinal infection in mice nor for filament formation in the gut. This is the first demonstration that the pathogenic attribute of dimorphism has biological facets unique to mucosal vs. systemic disease. The investigators propose a series of molecular genetic studies to define the mechanism(s) governing the development-specific expression of HWP1 in vitro and in vivo and the function of the encoded protein in hyphal development. These studies are set forth with the long-term objective of understanding the molecular basis of pathogenesis by C. albicans and that this knowledge may contribute to better approaches to disease prevention and treatment.

描述：（改编自申请人摘要）白色念珠菌是一种 艾滋病患者的机会致病菌。这些人通常会发展 口腔和食道感染。最近，念珠菌血症 已被认为是艾滋病患者的医院并发症， 显著相关死亡率。长期和预防性抗真菌药物 艾滋病患者的治疗导致了临床上的出现， 抗性C.白色念珠菌菌株。这一情况因有限的 有效的药物库。C.的生物学特性。白色念珠菌未知 部分原因是过去在基因操作方面遇到的困难， 真菌然而，大量的数据表明， 梭白色念珠菌在疾病的发展。在C.白色念珠菌， 二型性指的是这种生物体的能力， （单细胞）或菌丝（多细胞丝状）形态。的 相对较新的发展方法，以克服许多技术， C.遗传解剖中存在的问题白色念珠菌现在允许更接近 对二型性在疾病中的作用进行的机理性研究。的目的 目前的建议是调查一个特定的遗传决定因素， C.白色念珠菌HWP 1基因HWP 1在筛选中分离， 仅以丝状形式表达的基因。需要HWP 1 在全身性疾病的小鼠模型中， 小鼠胃肠道感染所需， 内脏这是第一次证明， 二态性具有粘膜疾病与系统性疾病所特有的生物学方面。的 研究人员提出了一系列的分子遗传学研究，以确定 控制HWP 1体外发育特异性表达的机制， 以及编码蛋白在菌丝发育中的功能。这些 研究的长期目标是了解 致病的分子基础。白色念珠菌，这些知识可能 有助于更好地预防和治疗疾病。