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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Research Project #441315

Research Project: Genomic and Mitigation Strategies to Control Mastitis

Location: Ruminant Diseases and Immunology Research

2023 Annual Report


Objectives
Objective 1: Compare Holstein cattle with a 1964 mastitis-resistant genetic background with modern mastitis-susceptible genetic background, identify genetic and immunologic traits that account for improved resolution of clinical mastitis against common mastitis pathogens and disease resistance through the periparturient period. Sub-objective 1.A: Compare the immune response to infection with Staphylococcus aureus between the two populations of Holsteins in both the acute and chronic phases of the disease. Sub-objective 1.B: Determine the impact of 1964 genetics on the proteome of innate immune cells during the periparturient period in comparison to cows with modern genetics. Objective 2: Facilitate the development of antibiotic alternatives to prevent and treat mastitis by identifying, isolating, and testing important components of bovine mammary gland dry secretions. Sub-objective 2.A: Fractionate components of mature bovine mammary gland dry secretions to identify portions that may be further developed as non-antibiotic mastitis preventive or treatment. Sub-objective 2.B: Determine if there are unique antimicrobial components to the 1964 cows’ dry secretion.


Approach
Mastitis is the most prevalent infectious disease in dairy herds and the costliest disease for dairy producers. Newer estimates of mastitis' economic impact on the dairy industry calculate a single clinical mastitis case costs an estimated $586. Antibiotics and proper cow management are the mainstays for mastitis treatment and control. Dairy cattle with mastitis plus antibiotic dry treatments account for more antibiotic usage than all other dairy cattle diseases combined. To reduce antibiotic use, we need to understand better how the immune system fails to eliminate mastitis infections. A unique resource, available through a collaboration with researchers at the University of Minnesota, is a herd of Holsteins that have not been subjected to selective breeding since 1964. These 1964 cows were compared to cows with modern genetics for their ability to respond to an experimental mastitis challenge with Escherichia coli. The 1964 cows were able to clear the infection almost immediately and had fewer clinical signs of infection. A long-term goal is to identify genetic traits that allow the 1964 cows' immune system to protect the host better. Identification of these immunological traits may allow us to bring back these immunological advantages into modern dairy cows. We will use experimental mastitis models, bacterial inhibition tests, and proteomic assays to determine differences between modern and 1964 cows' ability to recognize and destroy pathogens. We will challenge cows with Staphylococcus aureus, isolate antibacterial components in dry secretion, and demonstrate protein changes between modern and 1964 cows during the periparturient period. Isolation and identification of traits that grant greater resistance to mastitis will be used to genetically breed for more resistant animals or products using isolated compounds as therapeutics.


Progress Report
One scientist has been on extended medical leave. The other SY position was filled in April 2023, and immediately went on paid parental leave. In support of Sub-objective 1.A: Compare the immune response to infection with Staphylococcus aureus between the two populations of Holsteins in both the acute and chronic phases of the disease, samples have been collected and stored for processing and data collection. The majority of data collection has been accomplished with some yet to be completed. In support of Sub-objective 1.B: Determine the impact of 1964 genetics on the proteome of innate immune cells during the periparturient period in comparison to cows with modern genetics, many animals have been bred and samples successfully collected. Additional animals have been bred and we expect more samples to be collected as animals calve. In support of Sub-objective 2.A: Fractionate components of mature bovine mammary gland dry secretions to identify portions that may be further developed as non-antibiotic mastitis preventive or treatment, progress on this Sub-objective begins in FY24. In support of Sub-objective 2.B: Determination of the antimicrobial potential of each cow’s dry secretion, we have begun processing samples by centrifugation. When finished samples will be divided into sub-samples for antimicrobial testing and proteomic analysis.


Accomplishments
1. Heritage Holsteins used to identify potential impacts of selective breeding over the past 60 years. It is no secret that in modern agriculture, plants and animals are bred for improvements in agronomic and commercial characteristics. However, there may be some side effects of this breeding, that merit investigation. ARS scientists in Ames, Iowa, showed that cows with 1964 background had a higher concentration of small proteins, known as Cytokines, in blood when compared to contemporary cows. Cytokines are responsible to interact with cells and are known to be involved in influencing the immune system. The 1964 cows represent U.S. Holsteins that have not been altered since the mid-1960s and provide opportunities for direct comparisons of contemporary cows with representatives of their ancestors to assess impacts of selection in U.S. Holsteins. The cytokine response differences warrant additional studies with the 1964 vs. contemporary model to identify immune function differences between the genotypes. Identification of genomic factors responsible for these immune function differences could be used to strengthen selection efforts to improve health traits of Holsteins.


Review Publications
Brink, A.A., Weber, W.J., Lippolis, J.D., Cole, J.B., Godden, S.M., Sevkora, A., Crooker, B.A. 2022. Effect of Holstein genotype on ex-vivo innate immune response to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) during the periparturient period. Veterinary Immunology and Immunopathology. 251. Article 110463. https://doi.org/10.1016/j.vetimm.2022.110463.
Mateescu, R.G., Sarlo Davila, K.M., Hernandez, A.S., Nunez Andrade, A., Zayas, G., Rodriguez, E., Dikmen, S., Rafiq, F., Oltenacu, P. 2023. Impact of Brahman genetics on skin histology characteristics with implications for heat tolerance in cattle. Frontiers in Genetics. 14. Article 1107468. https://doi.org/10.3389/fgene.2023.1107468.