Antibiotics Discovery from the Great Lakes

从五大湖发现抗生素

• 批准号: 7241147
• 负责人: Eric Yiqiang Cheng
• 金额: $ 7.39万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7241147
• 关键词: Actinobacteria class; Actinomyces; Antibiotics; Antineoplastic Agents; Biological Factors; Bioterrorism; Categories; Chemicals; Detection; Emerging Communicable Diseases; Environment; Fermentation; Foundations; Future; Goals; Habitats; Hand; Hospitals; Location; Medicine; Michigan; Molecular; Nature; Oceans; Pharmaceutical Preparations; Phenotype; Pilot Projects; Process; Production; Protocols documentation; Rain; Rate; Recombinant DNA; Renaissance; Research; Research Personnel; Resistance; Resources; Ribosomal DNA; Sampling; Site; Solid; Standards of Weights and Measures; Students; System; Workload; drug discovery; experience; forest; fungus; liquid chromatography mass spectrometry; microbial; microorganism; novel; rRNA Genes; success

DESCRIPTION (provided by investigator): Antibiotics Discovery from the Great Lakes - New antibiotics are urgently needed to combat against many persistent, emerging and re-emerging infectious diseases, hospital-acquired resistance and bioterrorism agents. Currently there is a renaissance of drug discovery from natural products. Exploration of the rich microbial diversity in largely untapped environments offers renewed hope for the discovery of novel antibiotics, anticancer agents and other drugs from nature. Our hypothesis is that the Great Lakes sediment harbors a plethora of microorganisms that includes actinomycetes and fungi, from which new bioactive natural products could be obtained. Our long-term goal is to systematically explore the microbial resource in the Great Lakes sediment as an untapped environment for the discovery of new antibiotics and other categories of drug candidates. The immediate goal of this ongoing pilot project is to establish and optimize protocols for the accomplishment of the following three specific aims, as a foundation for future large-scale exploration: 1. To identify microbial isolates from Lake Michigan sediment by small-subunit rRNA gene (SSU rDNA) amplification and sequencing. Standard molecular taxonomic analysis will be employed to reveal the diversity and identification of isolated microorganisms, which in turn will facilitate the downstream microbial fermentation for optimal natural product production. 2. To dereplicate microbial extracts by liquid chromatography-mass spectrometry (LC-MS). Dereplication is a critical process in reducing the workload and increasing the success rate. LC-MS is regarded as one of the most appropriate and affordable approaches for extract dereplication because LC-MS analysis is a direct detection of the chemical phenotypes (metabolite profiles). 3. To purify and identify natural product(s) with antibiotic activities. Acquisition of antibiotic natural product(s) (either known or novel) will validate this pilot project and will lay a solid foundation for future large-scale exploration of the Great Lakes for new antibiotics and other categories of drug candidates. This pilot project serves as a proof-of-principle. Protocols established in this project will be extrapolated to other sampling sites in Lake Michigan, as well as other Great Lakes. This project provides ample opportunities for undergraduate students and graduate students to gain hands-on research experience. Relevance: The goal of this proposed project is to explore the Great Lakes sediment as an untapped environment for the discovery of microbial species from which new antibiotics may be obtained to combat against many persistent, emerging and re-emerging infectious diseases, hospital-acquired resistance and bioterrorism agents.

描述（研究者提供）：来自五大湖的抗生素发现——迫切需要新的抗生素来对抗许多持续存在的、新出现的和再出现的传染病、医院获得性耐药性和生物恐怖主义制剂。目前，从天然产物中发现药物的复兴。在大量未开发的环境中探索丰富的微生物多样性，为从自然界发现新的抗生素、抗癌药物和其他药物提供了新的希望。我们的假设是，五大湖沉积物中含有大量的微生物，包括放线菌和真菌，从中可以获得新的生物活性天然产物。我们的长期目标是系统地探索五大湖沉积物中的微生物资源，作为发现新抗生素和其他类别候选药物的未开发环境。这个正在进行的试点项目的直接目标是建立和优化协议，以实现以下三个具体目标，作为未来大规模勘探的基础：目的通过小亚单位rRNA基因（SSU rDNA）的扩增和测序，鉴定密歇根湖沉积物中分离的微生物。标准的分子分类分析将揭示分离微生物的多样性和鉴定，从而为下游微生物发酵提供便利，以获得最佳的天然产物。2. 采用液相色谱-质谱法（LC-MS）分离微生物提取物。重复复制是减少工作量和提高成功率的关键过程。由于LC-MS分析可以直接检测化学表型（代谢物谱），因此LC-MS被认为是最合适和负担得起的提取重复方法之一。3. 纯化和鉴定具有抗生素活性的天然产物。抗生素天然产物（无论是已知的还是新的）的获得将验证这一试点项目，并将为未来在五大湖大规模探索新的抗生素和其他类别的候选药物奠定坚实的基础。这个试点项目是一个原理证明。在这个项目中建立的协议将被推广到密歇根湖以及其他五大湖的其他采样点。这个项目为本科生和研究生提供了充分的机会来获得实践研究经验。