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: 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
• 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

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通过针对真菌独有的主要调节基因来研究可能的分子策略，以控制真菌病原体对人类健康的有害影响。在此提案中，PI将重点放在人类病原体，曲霉曲霉。调节信号基因在真菌物种中往往是保守的。 PI的实验室组已证明Velvet或VEA是一个全球调节基因，可控制曲霉属物种中的形态发展和次生代谢，以及梭形菌群中真菌属的跨性别属。有趣的是，VEA仅在真菌中发现。曲霉曲霉已成为一种重要的人类病原体，其死亡率很高。 VEA缺失会影响不同的细胞过程的事实表明，VEA也可能是烟曲霉多因素发病机理的关键因素。 PI打算通过研究VEA依赖性化合物，尤其是二级代谢产物，探索烟曲霉中的作用，这可能导致真菌疾病。在此提案中，在鼠类感染模型中也将直接评估VEA突变菌株的毒力。这些基础研究将为控制人类病原体的潜力提供基础。 公共卫生相关性：VEA是真菌独有的全球监管基因，它控制着曲曲霉和其他真菌属中的发展和次要代谢。我们将通过研究VEA依赖性化合物，例如可能有助于疾病的二级代谢产物，探索病原曲霉中的VEA。 VEA在毒力中的作用也将通过鼠感染直接评估。