Location: Animal Health Genomics
Project Number: 3040-32000-036-000-D
Project Type: In-House Appropriated
Start Date: Nov 16, 2021
End Date: Nov 15, 2026
Objective:
Objective 1. Elucidate genotypic and phenotypic factors affecting host susceptibility to viral and bacterial pathogens associated with bovine respiratory disease complex (BRDC) in order to rationally design tools and approaches for increasing host resilience.
Sub-objective 1A: Genomic comparisons of BVDV-susceptible and -resistant bovine cell lines to identify host factors required for virus entry.
Objective 2. Elucidate virulence mechanisms of BRDC pathogens to rationally design effective strategies that reduce antibiotic use in the prevention and treatment of BRDC.
Sub-objective 2A: Reducing bovine CD18 binding to bacterial leukotoxin.
Sub-objective 2B: Identify outer membrane proteins of BRD bacterial pathogens suitable for vaccine testing and development.
Objective 3. Develop alternatives to antibiotics for the prevention and treatment of BRDC.
Sub-objective 3A: Identify changes in immune cell populations and the respiratory microbiome associated with administering probiotics to feeder cattle.
Approach:
Infectious respiratory diseases of ruminants are a serious health and economic problem for U.S. agriculture. In cattle alone, the costs of bovine respiratory disease complex (BRDC) exceed one billion dollars annually. Our project vision is to reduce the prevalence and severity of respiratory diseases, thereby promoting livestock welfare, enhancing producer efficiency, and reducing antibiotic use. BRDC is a multi-component disease caused by complex interactions among viral and bacterial pathogens, stress and environmental factors, and host genetics. Consequently, we have developed a multi-component approach focused on the host-pathogen interface to study respiratory disease. On the host side, a whole genome sequencing approach, combined with in vitro cell line gene-editing, will be used to identify bovine genes affecting susceptibility to bovine viral diarrhea virus infections. In addition, novel bovine CD18 sequences will be tested in vitro for reduced binding to bacterial leukotoxin, a major pathological cause of BRDC pneumonia. The impact of toxin-resistant CD18 sequences on cellular health will be tested with gene-editing approaches focused on cell lines. On the bacterial pathogen side, genomics will be used to identify and compare outer membrane proteins of Histophilus somni, Mannheimia haemolytica and Pasteurella multocida that could be developed into vaccines. Lastly, our approach will measure changes in the immune cell population and the respiratory microbiome associated with administering probiotics to feeder cattle. The knowledge gained from this research will be useful in developing new intervention strategies for controlling BRDC and producing healthier livestock, and could ultimately benefit animals, producers, veterinarians, diagnostic laboratories, pharmaceutical companies, genetic testing laboratories, and regulatory agencies.
