Identification of potential vaccine targets in livestock-associated Staphylococcus aureus

Mastitis, an infection of the mammary glands, is a common livestock disease. The bacterium Staphylococcus aureus is the principal cause of mastitis. Bovine mastitis results in large economic losses for farmers and the dairy industry due to decreased milk production, veterinary treatment costs, early livestock culling and preventive measures. Importantly, mastitis can pose a risk to public health due to the potential ingestion of bacterial toxins by consumers, residual antibiotics used to treat cows, and transmission of S. aureus among livestock and humans. Frequent interspecies transmissions between livestock and farmers underscore this view. The subsequent bacterial adaptations to a new host are facilitated by the horizontal transfer of mobile genetic elements (MGEs) carrying genes for virulence, immune evasion and antimicrobial resistance. Effective vaccines are highly desirable to fight bovine mastitis, but they do not yet exist. Since proteins exposed on the bacterial cell surface are attractive targets for immunization approaches, the research documented in this PhD thesis identified candidate vaccine targets through an integrated genomics, immunoproteomics and immunological approach. Special attention was attributed to S. aureus isolates from Mexican cows with mastitis, where potential vaccine targets and the role of MGEs in antibiotic resistance and virulence were investigated. The results show that particular exposed domains of proteins from the bacterial cell surface are attractive candidates for inclusion in a vaccine against bovine mastitis. Altogether, the research presented in this thesis shows that combined proteo-genomic and immunological analyses provide relevant leads for developing future subunit vaccines against staphylococcal infections in livestock