Development of Anti-Microbial Peptide Therapeutics

A safe food supply is critical to the well being of any society. However, in highly urbanized societies, the number of people affected by a contaminated food source can be huge. Antibiotic resistant disease in the U.S. is an escalating problem [2, 3]. Much of this problem is a result of the use of antibiotics in production animals, where they prevent disease. Chronic use results in the emergence of organisms resistant to the antibiotics. This project addresses this problem through the development of a new class of antimicrobials, based on totally different mechanisms of action than antibiotics.The rapid emergence of antibiotic-resistant strains of bacteria poses a threat to humans and other animals. This is particularly true in production animals that are housed in close quarters, where infections are easily spread. Antibiotics are not naturally found in animals, but rather are typically products of bacteria themselves, secreted to prevent the growth of other microorganisms. A potential solution to this problem of antibiotic resistance has attracted considerable interest: developing antimicrobials based on mammalian innate immunity peptides and proteins. Innate or non-specific immune response to infection is coded within the genome of plants and animals. In its most simple form it involves the rapid production of peptides and/or proteins (e.g. host defense molecules) that use multiple contact/penetration and intracellular mechanisms to rapidly destroy invading organisms.The Specific Aims of this project are to design antimicrobials based on the mammalian innate immunity class of peptides. Peptides are small molecules that are used for many purposes in the body of humans and other animals. While peptides are not typically used as drugs, due to their lack of oral activity and short duration of action, we have solved these problems. Through the use of new peptide design techniques we have made peptides that act as drugs; possessing oral activity with an extended duration of action. We are proposing to make one or more peptide antimicrobials to address different types of bacterial infections.In addition, many peptides classes show structural similarities, suggesting a common evolutionary origin. Innate immunity peptides have similar features to a class of peptides that regulate feeding and weight gain. We believe it will be possible to produce antimicrobial peptides that also have the ability to stimulate food intake, weight gain, and produce an overall more efficient utilization of feed. These would be highly desirable features for the food animal industry.