Identification of Staphylococcus aureaus Virulence Factors Associated with Bovine Mastitis
Authors: Sordillo Lorraine , Wojchowski Don , Perdew Gary , Saran Arthur , Leitner Gabriel 
Published: December 2021

Staphylococcus aureus is a major cause of mastitis in dairy cattle. The organism is able to adhere to and penetrate mammary epithelium, forming deep seated abscesses that result in chronic infections. This study was based on the observation that certain genotypes of S. aureus are isolated more frequently from field cases of bovine mastitis than others and the most prevalent genotypes of S. aureus have an increased ability to resist neutrophil phagocytosis and killing compared to the rare variants. It was hypothesized that these predominating genotypes differentially express virulence factors that allow them to overcome or suppress essential host defense mechanisms and successfully colonize mammary parenchyma. The overall objective of this study was to determine the mechanisms by which predominating S. aureus genotypes were able to resist mammary gland defense mechanisms. The following specific aims were accomplished to address the overall objectives of this project: 1. Analyze and compare cell surface and secreted protein profiles of common and rare S. aureus genotypes isolated from field cases of bovine mastitis. 2. Purify and sequence selectively synthesized proteins unique to the most prevalent genotypes of S. aureus . 3. Determine the in vitro effects of isolated proteins on essential host defense mechanisms. Results from each specific aim showed that these redominating genotypes differentially express factors that may allow them to overcome or suppress essential host defense mechanisms and successfully colonize mammary parenchyma. Using complementary approaches, both the US and Israeli teams identified differentially expressed S. aureus factors that were positively correlated with virulence as determined by the ability to modify host immune cell responses and increase disease pathogenesis. Several candidate virulence factors have ben identified at both the molecular (US team) and protein (Israeli team) levels. Components of the phosphotransferase system were shown to be differentially expressed in prevalent strains of S. aureus and to modify the growth potential of these strains in a milk microenvironment. Evidence provided by both the Israeli and US teams also demonstrated a potential role of Staphylococcal enterotoxins in the pathogenesis of mastitis. Certain enterotoxins were shown to directly affect neutrophil bactericidal activities which can profoundly affect the establishment of new intramammary infections. Other evidence suggests that S. aureus superantigens can suppress mammary defenses by enhancing lymphoid suppressor cell activity. Collectively, these data suggest that unique factors are associated with predominating S. aureus genotypes that can affect in vitro and in vivo virulence as related to the pathogenesis of bovine mastitis. The potential development of a subunit mastitis vaccine which incorporates only relevant antigenic determinants has not been investigated in depth. Experiments outlined in this proposal has identified putative virulence factors which contribute to the pathogenesis of S. aureus mastitis and which may be used to formulate an efficacious subunit mastitis vaccine. Results from these studies may lead to the development of new methods to prevent this costly disease, providing a viable alternative to less effective mastitis control procedures based on chemotherapy.