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.
Antibiotic resistant pathogens represent a major health issue. Here, we propose employing an innovative discovery platform to discover novel, effective, and safe antimicrobial drugs. Further, our approach will focus on Streptomyces symbiotic bacteria from insects, which represent a rich source of new antimicrobials stemming from their ecological role in mediating pathogen dynamics associated with their insect host.