Antibiotics Discovery from the Great Lakes

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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.