Study of the veA Gene in the Human Pathogen Aspergillus fumigatus

人类病原菌烟曲霉veA基因的研究

基本信息

批准号：
8238280
负责人：
Baohua Wang
金额：
$ 7.25万
依托单位：
NORTHERN ILLINOIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-15 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8238280
关键词：
Accounting Affect Aflatoxins Animals Aspergillosis Aspergillus Aspergillus fumigatus Aspergillus nidulans Cell physiology Cells Chemicals Collaborations Communication Data Defect Development Diagnosis Disease Disease Attributes Foundations Fungi Model Fusarium Future Genes Genetic Gliotoxin Goals Growth HIV Health Hematologic Neoplasms Homologous Gene Human Immune response Immunocompromised Host Immunosuppressive Agents Infection Investigation Knowledge Laboratories Letters Metabolic Metabolism Modeling Molecular Morphogenesis Mus Mycelium Organ Transplantation Organism Pathogenesis Pathogenicity Patients Plants Production Property Publishing Regulator Genes Research Role Seedling Seeds Signal Transduction Sterigmatocystin System Therapeutic United States National Institutes of Health Virulence Work chemotherapy clinically significant cytotoxic experience fumigatin fumitoxins fungus helvolic acid mortality mutant pathogen public health relevance research study tissue culture tryptoquivaline

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this project is to investigate possible molecular strategies to control the detrimental effects of fungal pathogens on human health by targeting major regulatory genes that are unique to fungi. In this proposal the PI will focus on the human pathogen, Aspergillus fumigatus. Regulatory signaling genes tend to be conserved among fungal species. The PI's laboratory group has demonstrated that velvet, or veA, is a global regulatory gene that controls both morphological development and secondary metabolism in species of the genus Aspergillus, and across fungal genera in Fusarium spp. Interestingly, VeA has only been found in fungi. Aspergillus fumigatus has emerged as an important human pathogen with high mortality rates for the inmmunosuppressed. The fact that deletion of veA affects different cellular processes suggests that veA could also be a key factor in A. fumigatus multifactorial pathogenesis. The PI intends to explore the role veA in A. fumigatus by study veA-dependent compounds, particularly secondary metabolites, which may contribute to fungal disease. In this proposal, virulence of the veA mutant strains will also be directly assessed in a murine infection model. These basic studies will provide an essential foundation into the potential of VeA- targeting to control human pathogens. PUBLIC HEALTH RELEVANCE: veA is a global regulatory gene unique to fungi that controls development and secondary metabolism in Aspergillus and other fungal genera. We will explore the role veA in the pathogenic A. fumigatus by studying veA-dependent compounds, such as secondary metabolites that may contribute to disease. The role of veA in virulence will also be directly assessed through murine infection.

描述（由申请人提供）：该项目的长期目标是研究可能的分子策略，通过针对真菌特有的主要调控基因来控制真菌病原体对人类健康的有害影响。在该提案中，PI 将重点关注人类病原体烟曲霉。调节信号基因在真菌物种中往往是保守的。 PI 的实验室小组已经证明，velvet（或 veA）是一种全局调控基因，可控制曲霉属物种以及镰刀菌属真菌属的形态发育和次生代谢。有趣的是，VeA 仅在真菌中发现。烟曲霉已成为一种重要的人类病原体，对于免疫抑制者来说死亡率很高。 veA 缺失会影响不同的细胞过程，这一事实表明 veA 也可能是烟曲霉多因素发病机制的关键因素。 PI 打算通过研究 veA 依赖性化合物，特别是可能导致真菌疾病的次生代谢物，探索 veA 在烟曲霉中的作用。在该提案中，还将在小鼠感染模型中直接评估 veA 突变株的毒力。这些基础研究将为 VeA 靶向控制人类病原体的潜力提供重要基础。公共卫生相关性：veA 是真菌特有的全局调控基因，控制曲霉属和其他真菌属的发育和次生代谢。我们将通过研究 veA 依赖性化合物（例如可能导致疾病的次级代谢产物）来探索 veA 在致病性烟曲霉中的作用。 veA 在毒力中的作用也将通过小鼠感染直接评估。