There is a critical and urgent need to develop novel therapeutics to treat infectious diseases. However, contemporary studies attempting to discover new antibiotics from the traditionally most productive source, soil Actinobacteria in the genus Streptomyces, result almost entirely in the rediscovery of already known compounds. Through close collaboration with the Clardy lab, our recent work has identified a rich, diverse, and largely untapped source of novel small molecules with therapeutic potential: Actinobacteria associated with insects. We have discovered over 20 novel natural products from chemical characterization of less than 200 insect-associated Actinobacteria—a success rate of novel small molecule discovery significantly greater than the estimated 1 new compound from 10,000 strains examined using traditional sources and approaches. Our findings further indicate that these insects utilize the Actinobacteria-derived compounds to inhibit specialized bacterial and fungal parasites/pathogens. This activity suggests that these insects have coevolved with symbiotic bacteria that are selected to produce biologically active small molecules that provide chemical defense. In AP3, we will contribute to the overall goal of this ICBG proposal to identify novel drug leads from bacterial symbionts of insects from Brazil, a new geographic setting for our discovery pipeline, through completion of three Specific Aims.
Specific Aim 1. Identify the diversity and specificity of symbiotic bacteria associated with Brazilian insect-bacterial symbioses to help guide ecological-based sampling for a productive natural product pipeline.
Specific Aim 2. Determine the antifungal inhibitory potential of symbiotic bacteria associated with Brazilian insect-bacterial symbioses to help identify strains with the ability or potential to produce biologically active small molecules.
Specific Aim 3. Train Brazilian biologists in methods associated with ecological-based approaches to identify bacterial symbionts that produce natural products.
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