Optimizing the microbiome of dairy cattle for increased resistance to Staphylococcus aureus colonization

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Bovine mastitis is bacterial infection in udders of dairy cattle that results in painful inflammation, a reduction in milk production, and costs the dairy farmers of Canada an estimated $665 million annually. Staphylococcus aureus is a leading cause of bovine mastitis both in Canada and world-wide. S. aureus mastitis infections are concerning because infections are long-lasting, recurrent, and difficult to effectively treat with antibiotics. Dairy farmers treat cows therapeutically and prophylactically with antibiotics to attempt to treat or prevent infections; however, the human health effects of antibiotic resistance are a growing international crisis, and it is unlikely that this practice will continue indefinitely. Some bacterial species that routinely colonize the teat canal and raw milk are not associated with infection in the cow and can also antagonize S. aureus growth. In earlier work, we identified Staphylocuccus xylosus and Aerococcus urinaeequi as being two such species. However, in some instances both S. xylosus and A. urinaeequi are also suspected etiological agents of bovine mastitis, and it is unclear if the type of relationship that S. xylosus and A. urinqeequi isolates have with their host is due to host factors (i.e. immune status or age) or underlying differences in virulence potential of the specific bacterial isolate. This project will attempt to answer this question. We hypothesize that select isolates of S. xylosus and A. urinaeequi are not mammary pathogenic, antagonistic towards S. aureus, and suitable probiotics for the prevention of S. aureus mastitis. We propose three interconnected specific objectives to provide answers to fundamental and applied questions necessitating the complementary expertise of the present team members. We will use 1- whole genome sequencing to determine if there are obvious genomic differences between S. xylosus and A. urinqeequi isolates; 2- in vitro co-culture assays to determine which isolates can directly antagonize the growth of S. aureus; and 3- use a mouse model to determine if isolates from healthy cows cause mastitis in mice. This project will bring together top researchers to conclusively elucidate the roles of S. xylosus and A. urinqeequi in udder health and disease.