Group A Streptococcus (GAS) is a common and versatile human pathogen causing a variety of diseases. One of the many virulence factors of GAS is the secreted pore-forming cytotoxin streptolysin O (SLO), which has been ascribed multiple properties, including inflammasome activation leading to release of the potent inflammatory cytokine IL-1β from infected macrophages. IL-1β is synthesized as an inactive pro-form, which is activated intracellularly through proteolytic cleavage. Here, we use a macrophage infection model to show that SLO specifically induces ubiquitination and degradation of pro-IL-1β. Ubiquitination was dependent on SLO being released from the infecting bacterium, and pore formation by SLO was required but not sufficient for the induction of ubiquitination. Our data provide evidence for a novel SLO-mediated mechanism of immune regulation, emphasizing the importance of this pore-forming toxin in bacterial virulence and pathogenesis.

中文翻译：

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链球菌溶血素 O 诱导 Pro-IL-1β 的泛素化和降解。

A 组链球菌 (GAS) 是一种常见且用途广泛的人类病原体，可引起多种疾病。GAS 的众多毒力因子之一是分泌的成孔细胞毒素链球菌溶血素 O (SLO)，它具有多种特性，包括炎性体激活导致从受感染的巨噬细胞释放强效炎性细胞因子 IL-1β。IL-1β 以无活性前体形式合成，通过蛋白水解裂解在细胞内激活。在这里，我们使用巨噬细胞感染模型来证明 SLO 特异性诱导 pro-IL-1β 的泛素化和降解。泛素化依赖于从感染细菌中释放的 SLO，并且需要 SLO 形成孔，但不足以诱导泛素化。