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Candida Glabrata Gene Activation During Mucosal Infection

粘膜感染期间光滑念珠菌基因激活

基本信息

批准号：
7759164
负责人：
Caroline Westwater
金额：
$ 18.07万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7759164
关键词：
Accounting Antifungal Agents Biology Candida Candida albicans Candida glabrata Candidiasis Cells Characteristics Chromatin Data Defect Diagnosis Disease Disseminated candidiasis Emerging Technologies Gastrointestinal tract structure Gene Activation Gene Expression Gene Expression Profile Genes Goals Growth Health Health Care Costs Human Immune response In Vitro Incidence Infection Kidney Knock-out Knowledge Laboratories Life Life Style Molecular Molecular Profiling Morbidity - disease rate Mus Mycoses Nature Pathogenicity Pattern Peptide Hydrolases Process Production Regulation Relative (related person)Resistance Reverse Transcriptase Polymerase Chain Reaction Role Saccharomyces cerevisiae Sampling Screening procedure Site Staging Stomach Stomach Content Systemic infection T-Lymphocyte Technology Testing Therapeutic Intervention Time Tissues Transcript Transgenic Organisms Triazoles United States Virulence Virulence Factors base clinically significant extracellular improved in vivo insight mortality novel pathogen prophylactic public health relevance therapeutic vaccine treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Fungal infections represent an important health problem in terms of morbidity, mortality, and health care costs. Candida species are responsible for the largest number of fungal infections, with the majority attributed to Candida albicans and Candida glabrata. Both pathogens produce a similar array of superficial mucosal and life-threatening systemic infections; however, in contrast to C. albicans, C. glabrata is innately resistant to the most important triazole class of antifungals and lacks many of the virulence factors implicated in C. albicans invasion of host tissues. To compound this problem, several studies have documented a substantial increase in the incidence of C. glabrata infections. Despite this emergence, the biology of C. glabrata is largely unexplored and the basis for pathogenicity is unclear. Our long-term goal is to understand the molecular mechanisms required for C. glabrata colonization, persistence, and infection of mammalian tissues. In this R21 proposal, we will use emerging technologies to investigate the global transcript profile of C. glabrata during murine candidiasis and identify genes associated with the infectious process. To our knowledge, this will be the first study to identify the transcriptional signature of C. glabrata within an infected host. We hypothesize that C. glabrata possesses a repertoire of virulence-associated genes that are induced specifically in vivo during colonization and invasion of host tissues. We propose to: 1) identify C. glabrata genes expressed in vivo; 2) determine the gene expression profile of C. glabrata colonizing and infecting murine tissue; 3) identify a subset of genes induced specifically in a stage- and/or tissue-specific manner, and 4) establish a role for infection-associated genes in C. glabrata pathogenicity. Screening for host-induced genes represents a strategy to identify novel virulence factors and define global expression patterns relevant to pathogens. This study will provide insight into the diverse aspects of the fungal-host interaction and an improved understanding of the pathogenic processes contributing to disease. PUBLIC HEALTH RELEVANCE: Our findings will impact current treatment strategies by identifying virulence factors that may be targeted for prophylactic and therapeutic intervention. Such knowledge will accelerate our ability to diagnose, treat, and control the number one fungal pathogen of humans.

描述（由申请人提供）：真菌感染在发病率、死亡率和医疗保健费用方面是一个重要的健康问题。念珠菌属引起真菌感染的数量最多，其中大多数归因于白色念珠菌和光滑念珠菌。这两种病原体都会产生一系列类似的浅表粘膜和危及生命的全身感染。然而，与白色念珠菌不同，光滑念珠菌对最重要的三唑类抗真菌药物具有天生的抗性，并且缺乏与白色念珠菌入侵宿主组织有关的许多毒力因子。使这个问题更加复杂的是，一些研究已经证明光滑念珠菌感染的发病率大幅增加。尽管出现了这种情况，光滑念珠菌的生物学在很大程度上尚未被探索，致病性的基础也不清楚。我们的长期目标是了解光滑念珠菌定植、持久性和感染哺乳动物组织所需的分子机制。在这个 R21 提案中，我们将使用新兴技术来研究鼠念珠菌病期间光滑念珠菌的整体转录谱，并鉴定与感染过程相关的基因。据我们所知，这将是第一项鉴定受感染宿主内光滑念珠菌转录特征的研究。我们假设光滑念珠菌拥有一系列毒力相关基因，这些基因在定植和入侵宿主组织期间在体内被特异性诱导。我们建议：1）鉴定光滑 C. glabrata 体内表达的基因； 2)确定光滑念珠菌定植并感染小鼠组织的基因表达谱； 3) 鉴定以阶段和/或组织特异性方式特异性诱导的基因子集，以及 4) 确定感染相关基因在光滑念珠菌致病性中的作用。筛选宿主诱导的基因代表了一种识别新毒力因子并定义与病原体相关的整体表达模式的策略。这项研究将深入了解真菌与宿主相互作用的各个方面，并加深对导致疾病的致病过程的理解。公共卫生相关性：我们的研究结果将通过确定可能作为预防和治疗干预目标的毒力因子来影响当前的治疗策略。这些知识将提高我们诊断、治疗和控制人类头号真菌病原体的能力。