Antibiotics Discovery from the Great Lakes

描述（由研究者提供）：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性、新出现和重新出现的传染病、医院获得性耐药性和生物恐怖主义因子。目前，从天然产物中发现药物正在复兴。在大部分未开发的环境中探索丰富的微生物多样性为发现新的抗生素，抗癌剂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。这一正在进行的试点项目的近期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：采用小亚基rRNA基因（SSU rDNA）扩增和测序技术对密歇根湖沉积物中分离的微生物进行鉴定。将采用标准分子分类学分析来揭示分离的微生物的多样性和鉴定，这反过来又将促进下游微生物发酵以获得最佳的天然产物生产。2.通过液相色谱-质谱法（LC-MS）对微生物浸提液进行重复测定。消除复制是减少工作负载和提高成功率的关键过程。LC-MS被认为是提取物去复制的最合适和最经济的方法之一，因为LC-MS分析是化学表型（代谢产物谱）的直接检测。3.纯化和鉴定具有抗菌活性的天然产物。抗生素天然产物（已知或新）的获得将验证这一试点项目，并将为未来大规模勘探五大湖的新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则证明。在这个项目中建立的协议将外推到密歇根湖的其他采样点，以及其他五大湖。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。 相关性：这一拟议项目的目标是探索五大湖沉积物作为一个未开发的环境，以发现微生物物种，从中可以获得新的抗生素，以对抗许多持续存在的、新出现的和重新出现的传染病、医院获得的耐药性和生物恐怖主义制剂。

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.