Antibiotics Discovery from the Great Lakes

描述(由研究人员提供)：抗生素在五大湖中的发现-迫切需要新的抗生素来对抗许多持续的、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。目前，从天然产品中发现药物的活动正在复兴。在很大程度上尚未开发的环境中探索丰富的微生物多样性，为从自然中发现新型抗生素、抗癌剂和其他药物带来了新的希望。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，从这些微生物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近期目标是建立和优化方案，以实现以下三个具体目标，作为未来大规模探索的基础：1.通过小亚基rRNA基因(SSU RDNA)扩增和测序鉴定密歇根湖沉积物中的微生物分离物。标准的分子分类分析将被用来揭示分离微生物的多样性和鉴定，这反过来将促进下游微生物发酵以获得最佳的天然产品生产。2.用液-质联用技术(LC-MS)分离微生物提取物。去复制是减少工作量和提高成功率的关键过程。由于LC-MS分析是对化学表型(代谢物图谱)的直接检测，因此LC-MS被认为是最合适和最经济的萃取物去还原方法之一。3.具有抗菌活性的天然产物(S)的纯化和鉴定。收购抗生素天然产物(S)(无论是已知的还是新颖的)将验证这一试点项目，并将为未来在五大湖地区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。这一试点项目是一种原则证明。该项目建立的方案将外推到密歇根湖以及其他五大湖的其他采样点。该项目为本科生和研究生提供了大量实践研究经验的机会。 相关性：这个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，从这些微生物物种中可以获得新的抗生素，以对抗许多持久的、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.