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There is a necessity for new antibiotic discovery due to bacteria becoming resistant to currently prescribed antibiotics. Evidence suggests certain populations of bacteria may act as sources for natural antibiotics. A mammalian neuropeptide that possess antibacterial activity and is highly expressed in the gut, called vasoactive intestinal peptide (VIP), and its G protein coupled receptors, designated VPAC1 and VPAC2, have been shown to cause significant gut microbiota composition changes when knocked out (KO). Therefore, we hypothesized that mice deficient for VIP signaling would be good candidates for exploring the existence of novel antibiotic-producing bacteria (APB). To this end, fecal material from wild type (WT), heterozygous (HET) and KO strains were plated on nutrient agar, incubated aerobically, and zones of inhibition against Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus were tested. Our results showed elevated numbers of previously characterized APB from both HET receptor strains, but not from WT or VIP HET strains. We conclude that reduction in VIP receptor signaling in the gut, as opposed to loss of the VIP ligand, elevates the frequency of aerobic APB. Future studies will also utilize VPAC1 and VPAC2 KO strains to mine for the existence of novel anaerobic APB, many of which have yet to be investigated and therefore represent a potential antibiotic 'treasure chest' waiting to be harvested., Benjamin Huber * (U), Caleb Laney, Manpreet Baines, Amanda Brooks, Jane Schuh, Angela Hodgson, and Glenn Dorsam Microbiological Sciences, North Dakota State University Support: Frank J. Cassel Research Award Corresponding [...]