Development of three murine models of Staphylococcus aureus infection to aid in the characterization of a broadly protective vaccine and elucidation of immune responses to different routes of infection (155.29)

Abstract

Abstract Staphylococcus aureus is a common etiological agent of nosocomial and community acquired infections. Pan-antibiotic resistant strains of S. aureus have emerged at an alarming rate, making vaccination an important defense against S. aureus. S. aureus causes a variety of infections that differ in route of infection and disease progression, but previous experimental vaccines have focused on only one type of infection. Hence, multiple animal models are an important tool in studying broadly protective S. aureus vaccines. We sought to develop several murine models that mimic both planktonic and biofilm-mediated S. aureus disease. We focused on three infections that are of the greatest concern: biofilm-mediated implant infection, skin and soft tissue infection (SSTI), and sepsis. We have reproducibly generated a local, chronic, biofilm-mediated implant infection in 100% of C57BL/6 mice, and have determined the minimum dose that results in a chronic infection rate of 100%. We have also made progress towards determining the LD50, maximum non-lethal dose, and minimum lethal dose of S. aureus in a BALB/c sepsis model, as well as reproducibly produced SSTI in BALB/c mice. We plan to use these models to elucidate the memory responses associated with each infection type, and to characterize putative vaccines. If protective immune responses are elicited after vaccination in each of these models, those antigens will be combined into a multivalent vaccine to be tested in all three models.