Identification of novel MDR antimicrobials from insect-Streptomyces symbioses

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Abstract To combat the constant emergence of multidrug-resistant pathogens, the discovery of structurally novel natural products with antimicrobial properties is a critical need. As part of the Wisconsin Antimicrobial Drug Discovery and Development Center, we will address the urgent need for new antimicrobial drug leads by exploiting an innovative source: Streptomyces symbionts of insects. In our preliminary work we have shown that these Actinobacteria represent a rich and largely untapped source of novel antimicrobials with therapeutic potential. For example, we have shown in vivo (murine) safety and efficacy against Gram-negative bacterial and fungal human pathogens for several dozen lead molecules. In addition, we have confirmed antifungal efficacy and safety in our FDA-enabling murine model for our drug lead Cyphomycin, a novel molecule we discovered from an insect-Streptomyces. In our approach, we will also apply new genomic and metabolomic approaches, along with ecologically-informed bioassays. Our research will help reinvigorate the antimicrobial discovery pipeline and identify new MDR active drug leads.