Evidence that staphylococcal superantigens promote within-patient bacterial persistence following post-operative surgical site infection.

Staphylococcus aureus is a predominant cause of post-operative surgical site infections and persistent bacteremia. Here, we describe a patient who experienced three episodes of S. aureus infection over a period of 4 months following a total knee arthroplasty. The initial bloodstream isolate (SAB-0429) was a clonal complex 5 (CC5) and methicillin-resistant S. aureus (MRSA), whereas two subsequent isolates (SAB-0485 and SAB-0495) were CC5 isolates but methicillin-sensitive S. aureus. The two latter isolates harbored a plasmid encoding three superantigen genes that were not present in the primary MRSA isolate. SAB-0485 and SAB-0495 both expressed the plasmid-encoded staphylococcal enterotoxin R exotoxin and demonstrated increased superantigen activity compared with SAB-0429. Compared to SAB-0429, the latter isolates also demonstrated an increased bacterial burden in a mouse bacteremia model that was dependent on increased interferon-γ production. Curing of the plasmid from SAB-0485 reduced this virulence phenotype. These findings suggest that the superantigen exotoxins may provide a selective advantage in chronic post-surgical infections.IMPORTANCEIn this study, we investigated bacterial isolates from a patient who experienced three recurrent S. aureus infections over a 4 month period following total knee arthroplasty. Genomic and phenotypic characterization of these isolates revealed that they all belonged to clonal complex 5, yet the latter two strains contained an additional plasmid encoding superantigen exotoxins. Subsequent experimental infection experiments in mice demonstrated that the plasmid-encoded superantigens exacerbated bacteremia by promoting liver abscess formation. These experiments suggest that despite appropriate antibiotic therapy, bacterial superantigens may be able to promote persistent infection following post-surgery.