Streptococcus pyogenes (group A Streptococcus [GAS]) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses.

中文翻译：

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T4菌毛促进定植的M4化脓性链球菌的定殖和免疫逃避表型。

化脓性链球菌（A组链球菌[GAS​​]）是一种重要的人类病原体，可引起多种疾病，并具有明显的全球发病率和死亡率。几乎所有的GAS分离物都表达一种表面透明质酸胶囊，一种有助于宿主定植并阻止吞噬细胞杀伤力的毒性决定簇。然而，最近的流行病学监测已报道了由未包囊的GAS引起的粘膜和浸润性感染的持续增加，这质疑了透明质酸胶囊在GAS发病机理中不可或缺的作用。在这项研究中，我们发现M4 GAS的菌毛不仅显着促进了对人类上呼吸道上皮细胞和角质形成细胞的生物膜形成，粘附和细胞毒性，而且还促进了人类全血的生存并在侵入性感染的鼠模型中提高了毒力。T4抗原 M4 GAS的菌毛主链蛋白在细菌表面结合触珠蛋白，触珠蛋白是感染和炎症后上调的丰富人类急性期蛋白。结合珠蛋白减少了未封装的M4 GAS对从活化的嗜中性粒细胞和血小板释放的抗菌肽的敏感性。我们的研究结果揭示了M4 GAS菌毛以前没有意识到的促进毒力的作用，部分是通过选择触珠蛋白的生物学来减轻宿主的抗微生物防御作用而介导的。