Vasoactive intestinal peptide receptor - 1 deficiency causes an increase in the frequency of antibiotic producing bacteria in mouse fecal samples

Abstract

Abstract New antibiotic discovery is critical because bacteria are becoming resistant to currently prescribed antibiotics. A mammalian gut peptide, vasoactive intestinal peptide (VIP), is highly expressed in the gut and possess antimicrobial activity. VIP binds two receptors, designated VPAC1 and VPAC2, and deficiency in all three have been shown to cause significant gut microbiota dysbiosis. 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, bacteria fecal samples from C57Bl/6 wild type (WT), and heterozygous (HET) and/or homozygous mutant (KO) VIP, VPAC1 and VPAC2 strains were used to test for zones of inhibition against escape pathogens. Our results showed that heterozygous VPAC1 mice resulted in the greatest increase in APB compared to WT controls, VIP or VPAC2 genetically altered strains. Initial taxonomic identification of APB from VPAC1 Het fecal samples reveled previously characterized aerobic bacteria. We conclude that reduction in VPAC1 receptor signaling in the gut, as opposed to loss of the VIP ligand or VPAC2 signaling, elevates the frequency of aerobic APB. Future studies will now focus on utilizing VPAC1 WT, HET and KO littermates to mine for the existence of novel anaerobic APB.