Our collaborative, undergraduate-driven research program utilizes cultivation of environmental bacteria, natural product isolation, and synthetic organic chemistry to rapidly discover and evaluate potential antibiotics. In our antibiotic isolation program, bacterial strains are cultured from various plant-, rhizosphere- and aquatic- environments throughout Western North Carolina and screened for antibiotic production using a high-throughput antagonism assay against Staphylococcus aureus and Escherichia coli. Metabolite induction via microorganism co-culture is used to activate cryptic biosynthetic gene clusters and enhance chemical diversity for drug discovery. To date, over 30 antibiotic-producing bacteria have been cultivated and identified. Antagonistic organisms include members of several common genera, including Pseudomonas, Serratia and Streptomyces, as well as less characterized groups including Janthinobacteria and Rahnella species. Using culture scale-up and extraction, active compounds have been isolated from Pseudomonas (antagonistic against Gram-positive and Gram-negative bacteria, as well as antifungal), Chromobacterium, Serratia, and Streptomyces (antagonistic against Gram-positive bacteria only), and structural identification of active compounds is currently underway. In our synthetic program, electronic and structural analogs of known antibacterial natural products pestalone and depsidones, both of which have moderate activity against Gram-positive bacteria (MIC = 1-10 μg/mL), have been synthesized in high yield to explore each natural product’s structure activity relationship profile.

Improving antibiotic drug discovery through bacterial co-culture and synthetic chemistry

251st National Meeting (2016)

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