ALCOHOL FERMENTATION AND ASPERGILLUS FUMIGATUS HYPOXIA ADAPTATION

酒精发酵与烟曲霉缺氧适应

• 批准号: 7721030
• 负责人: Robert Andrew Cramer
• 金额: $ 15.42万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721030
• 关键词: Alcohol consumption; Alcohols; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cell Respiration; Computer Retrieval of Information on Scientific Projects Database; Condition; Data; Disease; Ethanol; Fermentation; Funding; Genetic; Grant; Hypoxia; Immunocompromised Host; Infection; Inflammatory Response; Institution; Invasive; Irrigation; Lung; Microbe; Molds; Mus; Mycoses; Organism; Oxidants; Oxygen; Pathogenesis; Pathway interactions; Pharmacotherapy; Production; Research; Research Personnel; Resources; Site; Source; United States National Institutes of Health; clinically significant; in vivo; metabolomics; mutant; pathogen

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aspergillus fumigatus is a saprophytic filamentous fungus that is increasingly becoming a significant opportunistic pathogen in immunocompromised patients. Currently, the mechanisms used by A. fumigatus to survive and cause disease in immunocompromised mammalian hosts is not understood. During mammalian pathogenesis, all pathogenic microbes are exposed to rapidly changing oxygen levels. Oxygen is the critical electron acceptor in aerobic respiration and organisms must possess alternative mechanisms to deal with low oxygen (hypoxic) conditions found at sites of infection in vivo. Dr. Cramer's hypothesis is that A. fumigatus utilizes an alcohol fermentation pathway to survive inflammatory responses found in vivo in pulmonary invasive aspergillosis. This hypothesis is founded on preliminary data from metabolomics studies of A. fumigatus infected murine broncheoalveolar lavages showing the production of ethanol in vivo during fungal infections. Dr. Cramer is exploring whether this alcohol fermentation pathway is important for A. fumigatus to cause disease by creating genetic mutants of A. fumigatus deficient in their ability to respond to low oxygen conditions via the use of an alcohol fermentation pathway. In addition, Dr. Cramer's lab is attempting to identify other mechanisms utilized by this pathogenic mould to adapt to hypoxic microenvironments found at sites of infection. The results of this proposal have potential clinical significance via direct manipulation of oxygen levels at sites of fungal infection, which may enhance the effects of current antifungal drug therapies.

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 烟曲霉是一种嗜酸性丝状真菌，在免疫功能低下的患者中日益成为一种重要的机会致病菌。目前，A.烟曲霉在免疫受损的哺乳动物宿主中存活并引起疾病的原因尚不清楚。在哺乳动物发病过程中，所有病原微生物都暴露在迅速变化的氧气水平中。氧是有氧呼吸中的关键电子受体，生物体必须具有替代机制来处理体内感染部位的低氧（缺氧）条件。Cramer博士的假设是A.烟曲霉菌利用酒精发酵途径在肺侵袭性曲霉病体内发现的炎症反应中存活。这一假说是建立在A.烟曲霉感染的小鼠支气管肺泡灌洗液显示在真菌感染期间体内乙醇的产生。Cramer博士正在探索这种酒精发酵途径是否对A.烟曲霉通过产生A.烟曲霉缺乏通过使用酒精发酵途径对低氧条件作出反应的能力。此外，Cramer博士的实验室正试图确定这种致病霉菌利用的其他机制，以适应感染部位的缺氧微环境。该建议的结果具有潜在的临床意义，通过直接操纵氧气水平在真菌感染的网站，这可能会提高目前的抗真菌药物治疗的效果。