Dysregulation of antimicrobial peptide gene expression

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The research addresses antibacterial responses of epithelial cells at body surfaces, and particularly how failure of these defences leads to development of opportunistic bacterial infections. Bacterial pneumonia is an important cause of economic loss in beef production, and a paradigm for studying the complex interactions among host, pathogens, and the environment. The proposed research investigates the activity of antimicrobial peptides against a range of bovine respiratory pathogens, and the stimuli that increase production of these natural antibacterial products. We previously observed that corticosteroids and viral infection impair the synthesis of these antimicrobial peptides, and this effect may mediate stress-related susceptibility to bacterial infection. This effect will be confirmed in vivo, and the intracellular signalling pathways responsible will be elucidated. The potential for artificial stimulation of these responses as a novel method to prevent bacterial pneumonia will be tested. Finally, the same response is investigated in the context of chytridiomycosis, an emerging fungal disease of frogs that is one reason for global declines and extinction of amphibian species. It is proposed that stress-related failure of antimicrobial peptide synthesis is a link between global climate change, local alteration of environmental conditions, and increased predisposition to this cutaneous infectious disease. These studies will elucidate whether and how a failure of antimicrobial peptide gene expression leads to two important diseases that appear to share many similarities--bacterial pneumonia in beef cattle, and chytridiomycosis in frogs. These findings are expected to lead to improved strategies to control this common disease in beef cattle, as well as an improved understanding of whether and how environmental influences affect susceptibility of frog populations to this emerging infectious disease.