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In Objective 1, we will investigate the antimicrobial potency and spectrum of novel antimicrobial peptides. <P>Objecitve 2 will address the structure-activity relationships of novel antimicrobial peptides. Lastly, we will evaluate the in vivo role of a selected antimicrobial peptide in protecting animals against infection.
Non-Technical Summary: The indiscriminate use of antibiotics for growth promotion and disease prevention in the food animal industry has been accompanied by contamination of food products and the environment with unwanted drug residues and rapid emergence of antibiotic-resistant microorganisms. This purpose of this study is to identify efficacious antimicrobial peptides that can be used as alternative non-antibiotic means to prevent and control various infectious diseases and to enhance preharvest food safety in the food animal industry. <P> Approach: Novel natural antimicrobial peptides that we discovered recently from farm animals will be selected for evaluation of their in vitro activity against a broad range of agriculturally important pathogen, including antibiotic-resistant strains. The tertiary structures of selected natural antimicrobial peptides will be determined by nuclear magnetic resonance (NMR) spectroscopy. Based on the three-dimensional structural information, additional peptide analogs will be strategically designed by altering the length, charge, helicity, and amphipathicity of the parent peptide. The derivatives will be chemically synthesized and compared for their antimicrobial activities. A peptide analog with potent antibacterial activities will be selected for delivery into food animals to study whether it confers protection against experimental infections with USDA high priority pathogens. We expect that the peptide acting efficaciously in vitro will be sufficient in alleviating pathology and the bacterial load in vivo.