Abscess Formation and Alpha-Hemolysin Induced Toxicity in a Mouse Model of Staphylococcus aureus Peritoneal Infection

Abstract

ABSTRACTStaphylococcus aureusis a frequent cause of skin infection and sepsis in humans. Preclinical vaccine studies withS. aureushave used a mouse model with intraperitoneal challenge and survival determination as a measure for efficacy. To appreciate the selection of protective antigens in this model, we sought to characterize the pathological attributes ofS. aureusinfection in the peritoneal cavity. Testing C57BL/6J and BALB/c mice, >109CFU ofS. aureusNewman were needed to produce a lethal outcome in 90% of animals infected via intraperitoneal injection. Both necropsy and histopathology revealed the presence of intraperitoneal abscesses in the vicinity of inoculation sites. Abscesses were comprised of fibrin as well as collagen deposits and immune cells with staphylococci replicating at the center of these lesions. Animals that succumbed to challenge harbored staphylococci in abscess lesions and in blood. The establishment of lethal infections, but not the development of intraperitoneal abscesses, was dependent onS. aureusexpression of alpha-hemolysin (Hla). Active immunization with nontoxigenic HlaH35Lor passive immunization with neutralizing monoclonal antibodies protected mice against early lethal events associated with intraperitonealS. aureusinfection but did not affect the establishment of abscess lesions. These results characterize a mouse model for the study of intraperitoneal abscess formation byS. aureus, a disease that occurs frequently in humans undergoing continuous ambulatory peritoneal dialysis for end-stage renal disease.