POLYOL METABOLITES OF PATHOGENIC FUNGI AS MARKERS FOR INFECTION

病原真菌的多元醇代谢物作为感染标志物

• 批准号: 3747032
• 负责人: BRIAN WONG
• 金额: --
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3747032
• 关键词: Aspergillus; Cryptococcus; Fungi; arabinose; biomarker; bone marrow transplantation; candidiasis; cerebrospinal fluid; communicable disease diagnosis; fluconazole; gas chromatography; heart transplantation; human subject; human tissue; laboratory rabbit; laboratory rat; leukemia; mannitol; meningitis; opportunistic infections

Candida produces large amounts of the polyol D-arabinitol in vitro, and body fluid D-arabinitol levels are high in animals and humans with invasive candidiasis. In preliminary experiments, three pathogenic Aspergillus species and Cryptococcus neoformans produced large amounts of the polyol D-mannitol in vitro, and animals with experimental aspergillosis and cryptococcosis had high body fluid D-mannitol levels. The specific aims of this project are to: 1) evaluate the D-mannitol as a potential quantitative marker for invasive aspergillosis; 2) evaluate D-mannitol as a potential marker for cryptococcosis; and 3) identify polyol products of other pathogenic fungi that may be markers for initial diagnosis, estimating fungal load, and assessing the results of treatment. D-mannitol will be measured by gas chromatography in the serum, urine and homogenized tissues of rats with disseminated and pulmonary aspergillosis: 1) to determine how often and when body fluid and tissue D-mannitol levels rise; 2) to correlate fungal D-mannitol production with severity of infection; and 3) to correlate the effects of antifungal therapy on fungal load and fungal D-mannitol production. D-mannitol will also be measured in sera from: 1) patients receiving intensive chemotherapy for acute leukemia or other neoplastic diseases at several Cincinnati hospitals, 2) all patients who have bone marrow transplants, heart transplants or autopsies at the University of Cincinnati, and 3) patients from our center and others who have proven presence or absence of invasive aspergillosis. D-mannitol will be evaluated as a potential quantitative marker for cryptococcosis by analyzing cerebrospinal fluid (CSF), serum and/or tissues of rabbits with experimental meningeal or disseminated cryptococcosis. The effects of renal failure, meningeal inflammation and antifungal therapy will also be studied. D-mannitol will also be measured in serial serum and/or CSF specimens from all patients with cryptococcosis at the University of Cincinnati, participants in two multicenter trials comparing amphotericin B and fluconazole as initial or maintenance therapies for cryptococcal meningitis, and appropriate controls. Lastly, production of distinctive polyols by other fungi will be studied in vitro, in experimentally infected animals and in humans. The long-term objective of this research is to examine the possibility that detection and quantitation of distinctive microbial metabolites in the body fluids is more broadly applicable as a general strategy for studying infectious diseases.

假丝酵母菌在体外产生大量多元醇D-阿拉伯糖醇，以及 在患有侵袭性疾病的动物和人类中，体液D-阿拉伯醇水平很高 念珠菌病。在初步实验中，三种致病曲霉 菌种和新生隐球菌产生大量的多元醇 D-甘露醇在体外，以及实验性曲霉病和 隐球菌病患者体液中D-甘露醇水平较高。的具体目标 本项目的目的是：1)评价D-甘露醇的开发潜力 侵袭性曲霉病的定量标记物；2)评价D-甘露醇作为 隐球菌病的潜在标记；以及3)鉴定隐球菌病的多元醇产品 其他可能作为初步诊断标志的病原真菌， 估计真菌负荷，并评估治疗结果。D-甘露醇 将用气相色谱测定的血清、尿液和匀浆 播散性和肺曲霉病大鼠的组织：1)至 确定体液和组织中D-甘露醇水平升高的频率和时间； 2)真菌产生D-甘露醇与感染严重程度的关系； 3)将抗真菌治疗对真菌负荷的影响与 真菌D-甘露醇生产。还将在血清中检测D-甘露醇 来自：1)接受急性白血病强化化疗的患者或 辛辛那提几家医院的其他肿瘤疾病，2)所有患者 有骨髓移植，心脏移植或尸检的人 辛辛那提大学，以及3)我们中心的患者和其他 已证实有或没有侵袭性曲霉病。D-甘露醇会 被评估为隐球菌病的潜在定量标记 脑脊液、血清和/或组织的分析 实验性脑膜或播散性隐球菌病。的影响 肾功能衰竭、脑膜炎和抗真菌治疗也将 学习。还将在系列血清和/或脑脊液中检测D-甘露醇 密歇根大学所有隐球菌病患者的样本 辛辛那提，两个比较两性霉素B的多中心试验的参与者 和氟康唑作为隐球菌的初始或维持治疗 脑膜炎和适当的对照。最后，特色产品的生产 其他真菌产生的多元醇将在体外进行研究，并在实验中感染 在动物和人类身上。这项研究的长期目标是 检查检测和定量区分的可能性 体液中的微生物代谢物更广泛地适用于 研究传染病的一般策略。