Staphylococcal enterotoxin B contributes to Staphylococcus aureus systemic infection.

Bae, Justin S; Da, Fei; Liu, Ryan; He, Lei; Lv, Huiying; Fisher, Emilie L; Rajagopalan, Govindarajan; Li, Min; Cheung, Gordon Y C; Otto, Michael

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB towards S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus (CA-MRSA) lineage ST59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting value of including SEB as a target in multi-pronged anti-staphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of CA-MRSA infection.