Title: Targeting bacterial-extracellular matrix interactions to construct a Staphylococcus aureus vaccine for bovine mastitis
Project Summary: Staphylococcus aureus is an important human bacterial pathogen as well as a major cause of infection in the udder, or mastitis, in dairy cattle.  Despite control measures and vaccine development efforts over the past two decades, S. aureus continues to cause significant human mortality and considerable economic loss for the dairy industry worldwide.  In bovines, S. aureus can establish chronic subclinical colonization of the udder that is highly transmissible and often undetected.  Subclinical disease is dependent upon bacterial interaction with host extracellular matrix (ECM) molecules such that S. aureus is able to establish intracellular growth.  The development of a vaccine to target S. aureus mammary gland chronic colonization and host cellular uptake in bovines would improve animal health, reduce agricultural dependence on antibiotics, and inform human vaccine development.  It is our objective to identify S. aureus surface proteins that are expressed in the bovine udder and that target the ECM for incorporation into a vaccine. We will characterize the role of these proteins in adhesion and cellular uptake in vitro, and in pathogenicity in vivo in the mouse model. We hypothesize that modern methods to identify and characterize S. aureus ECM-binding adhesins will promote the development of an effective multivalent bovine vaccine for mastitis that will have dual benefit in biomedicine and agriculture. Specifically, we propose to: 1) utilize proteomics and transcriptomics to identify bovine ECM-binding S. aureus vaccine antigens, 2) construct isdA S. aureus deletion mutants to define IsdA-cellular and ECM interactions in vitro, and 3) utilize a mouse model to define the contribution of IsdA in the pathogenesis of mastitis.  These studies represent advancements toward the development of a bovine S. aureus vaccine through the identification and characterization of antigens involved in bacterial-host interactions. Long term goals are expected to have positive impacts on both animal and human health.