Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
J Infect Dis. 2021 May 28;223(10):1766-1775. doi: 10.1093/infdis/jiaa584.
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 to 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 lineage sequence type (ST) 59 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 the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection.
金黄色葡萄球菌肠毒素 B（SEB）由主要的人类病原体金黄色葡萄球菌产生，是一种强大的超抗原毒素，被认为是一种生物武器。然而，在临床相关菌株的遗传定义突变体中，从未直接证明 SEB 对金黄色葡萄球菌发病机制的贡献。主要的亚洲社区相关耐甲氧西林金黄色葡萄球菌谱系序列型（ST）59 的许多分离株都携带 seb，这意味着 SEB 在观察到该谱系的高致病性中具有重要作用。我们在一个具有代表性的 ST59 分离株中创建了 seb 基因的同源缺失突变体，并在小鼠感染模型中评估了其毒力潜能。我们检测到 seb 对全身性 ST59 感染有显著贡献，这与细胞因子风暴有关。我们的结果直接证明了 seb 有助于金黄色葡萄球菌发病机制，这表明将 SEB 作为多管齐下的抗葡萄球菌药物开发策略的目标具有重要意义。此外，它们表明 seb 有助于社区相关耐甲氧西林金黄色葡萄球菌感染的致命恶化。
