Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection
Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection
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DOI：
10.1093/infdis/jiaa584
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发表时间：
2021-05-15
影响因子：
6.4
通讯作者：
Otto, Michael
中科院分区：
文献类型：
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作者：
Bae, Justin S.;Da, Fei;Otto, Michael
金黄色葡萄球菌肠毒素B（SE B）是由金黄色葡萄球菌（Staphylococcus aureus）产生的一种强有力的超抗原毒素，被认为是一种生物毒素。然而，SEB对S.金黄色葡萄球菌的发病机制从未在临床相关菌株中用遗传确定的突变体直接证明。许多主要的亚洲社区相关的耐甲氧西林S。金黄色葡萄球菌谱系序列型（ST）59携带SEB，这意味着SEB在观察到的该谱系的高毒力中起重要作用。我们在代表性的ST 59分离株中创建了一个同基因seb突变体，并在小鼠感染模型中评估了其毒力潜力。我们检测到seb对系统性ST 59感染的显著贡献，其与细胞因子风暴相关。我们的结果直接证明了seb对S.金黄色葡萄球菌的发病机制，表明包括SEB作为一个目标，多管齐下的抗葡萄球菌药物开发策略的价值。此外，他们指出，seb有助于社区相关的耐甲氧西林沙门氏菌的致命性恶化。金黄色葡萄球菌感染。
Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigcnic toxin and is considered a biowcapon. 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.