PROJECT SUMMARY Key metabolites from microbiota, probiotics and diet can inhibit the virulence properties of enteric pathogens, but their mechanisms of action are unclear and limit the development of new anti-infectives. To determine the mechanism(s) of action of prominent microbiota metabolites (short chain fatty acids, aromatic amino acids, bile acids and others), multi-disciplinary approaches are needed to biochemically identify metabolite-protein targets in enteric pathogens and characterize their activity on infections in vivo. My laboratory will therefore employ innovative methods in chemical biology, proteomics and gene editing in bacteria to elucidate how specific metabolites attenuates enteric pathogen infections. A better understanding of how these metabolites affects the virulence properties of bacterial pathogens should reveal potential therapeutic targets and facilitate the development of new anti-infectives to combat bacterial pathogens in animals and humans.