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: 3803879
• 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/3803879
• 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.

假丝酵母在体外产生大量的多元醇D-阿拉伯糖醇， 体液D-阿拉伯糖醇水平在动物和人类中很高， 念珠菌病 在初步实验中，三种致病曲霉 种和新型隐球菌产生大量的多元醇 D-甘露醇在体外，和动物与实验曲霉菌病和 隐球菌病患者的体液D-甘露醇水平较高。 的具体目标 本项目的目的是：1）评价D-甘露醇作为一种潜在的 侵袭性曲霉病的定量标志物; 2）评估D-甘露醇作为 隐球菌病的潜在标志物;和3）鉴定 其他病原真菌可能是初步诊断的标志物， 估计真菌负荷，并评估治疗结果。 甘露醇 将通过气相色谱法测定血清、尿液和匀浆中的 播散性肺曲霉病大鼠的组织：1） 确定体液和组织D-甘露醇水平升高的频率和时间; 2)将真菌D-甘露醇的产生与感染的严重程度相关联; 和3）将抗真菌治疗对真菌负荷的影响与 真菌D-甘露醇生产。 还将测量血清中的D-甘露醇 来自：1）接受急性白血病强化化疗的患者，或 其他肿瘤疾病在几个辛辛那提医院，2）所有患者 进行骨髓移植、心脏移植或尸检的人 辛辛那提大学，以及来自我们中心的患者和其他 已证实存在或不存在侵袭性曲霉病。 D-甘露醇将 作为隐球菌病的潜在定量标志物， 分析兔的脑脊液（CSF）、血清和/或组织， 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 研究了 还将在连续血清和/或CSF中测量D-甘露醇 所有隐球菌病患者的标本， 辛辛那提，两个多中心试验的参与者比较了阿替霉素B 和氟康唑作为隐球菌感染的初始或维持治疗 脑膜炎和适当的控制。 最后，生产特色 多元醇的其他真菌将在体外研究，在实验感染 动物和人类。 这项研究的长期目标是 研究检测和定量不同的 体液中的微生物代谢物更广泛地适用于作为 研究传染病的一般策略。