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The overall objective of this application is to evaluate the potential for dietary modulation of antimicrobial peptide (AMP) synthesis in the control of necrotic enteritis in the chicken. <P>
Three specific objectives are to: <OL> <LI> screen for the dietary factors that are capable of inducing chicken AMP gene expression<LI> study molecular mechanisms by which chicken AMPs are processed into biologically active forms<LI> evaluate the efficacy of oral administration of a dietary factor in the protection of chickens from Clostridium perfringens infections </ol>This project will lead to identification of the dietary factors that are capable of augmenting animal innate immunity and disease resistance with no reliance on antibiotics, which will also be broadly applicable in the control and prevention of all major pathogens in other food animal species.
NON-TECHNICAL SUMMARY: Clostridium perfringens, the etiological agent of necrotic enteritis and a USDA high priority pathogen, continues to cause significant economic losses to the poultry industry and also poses considerable public health concern as one of the most common foodborne pathogens. Strategies on the prevention and reduction of this pathogen are urgently needed. Broadly effective against virtually all classes of pathogens, antimicrobial peptides (AMPs) offer a new concept of disease control. Synthesis of several of these AMPs was recently shown to be specifically augmented by certain short chain fatty acids, vitamin D3, and essential amino acids, providing the rationale for boosting innate immunity and disease resistance by convenient dietary modulation of endogenous AMP production. The long-term goal of our research is to explore the potential for natural AMPs in the control and prevention of diseases of agricultural importance. This research may lead to the development of a truly innovative, cost-effective strategy in disease control and prevention for all food animal species, offering great potential of enhancing animal biosecurity and production efficiency, while minimizing the use of antibiotics and emergence of drug-resistant pathogens.<P>APPROACH: A range of dietary factors, including short chain fatty acids, vitamins, essential amino acids, and trace minerals will be screened individually or in combination for their ability to induce antimicrobial peptide (AMP) gene expression and to promote AMP processing and maturation. We will also attempt to identify the mature forms of two representative chicken AMPs by reverse-phase HPLC, mass spectrometry, and N-terminal sequencing. The dietary factor(s) that are most potent in promoting AMP synthesis and/or maturation will then be orally administered into chickens following experimental infections with Clostridium perfringens. Intestinal pathology and bacterial titer will be examined, and AMP gene expression in the intestinal tract will be monitored as well. We expect that appropriate dietary treatments will enhance AMP production and resistance to C. perfringens colonization and pathology.