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

• 批准号: 8113847
• 负责人: ANA M CALVO-BYRD
• 金额: $ 7.25万
• 依托单位: NORTHERN ILLINOIS UNIVERSITY
• 依托单位国家: 美国
• 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/8113847
• 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; research study; tissue culture; tryptoquivaline

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）：本项目的长期目标是研究可能的分子策略，通过靶向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。在本提案中，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趋于保守。PI的实验室小组已经证明，天鹅绒，或veA，是一个全球性的调控基因，控制形态发育和次生代谢的曲霉属的物种，并跨越真菌属的镰刀菌属。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，对免疫抑制者具有高死亡率。veA的缺失影响不同的细胞过程这一事实表明，veA也可能是A.烟曲霉多因素致病PI打算探索veA在A中的作用。通过研究veA依赖的化合物，特别是次级代谢产物，这可能有助于真菌病。在该提议中，还将在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必要的基础。 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。我们将探讨veA在致病性A中的作用。通过研究veA依赖性化合物，如可能导致疾病的次级代谢产物，研究烟曲霉。还将通过鼠感染直接评估veA在毒力中的作用。