Staphylococcus aureus (S. aureus) is a leading human pathogen capable of producing severe invasive infections such as bacteremia, sepsis, and endocarditis with high morbidity and mortality, exacerbated by the increasingly widespread antibiotic resistance exemplified by methicillin-resistant strains (MRSA). S. aureus pathogenesis is fueled by the secretion of toxins—such as the membrane-damaging pore-forming α-toxin, which have diverse cellular targets including the epithelium, endothelium, leukocytes, and platelets. Here, we examine the use of human platelet membrane-coated nanoparticles (PNPs) as a biomimetic decoy strategy to neutralize S. aureus toxins and preserve host cell defense functions. The PNPs blocked platelet damage induced by S. aureus secreted toxins, thereby supporting platelet activation and bactericidal activity. Likewise, the PNPs blocked macrophage damage induced by S. aureus secreted toxins, thus supporting macrophage oxidative burst, nitric oxide production, and bactericidal activity, and diminishing MRSA-induced neutrophil extracellular trap release. In a mouse model of MRSA systemic infection, PNP administration reduced bacterial counts in the blood and protected against mortality. Taken together, the results from the present work provide a proof of principle of the therapeutic benefit of PNPs in toxin neutralization, cytoprotection, and increased host resistance to invasive S. aureus infection.

金黄色葡萄球菌( S. aureus ) 是一种主要的人类病原体，能够产生严重的侵袭性感染，例如具有高发病率和死亡率的菌血症、败血症和心内膜炎，并因日益广泛的抗生素耐药性而加剧，例如耐甲氧西林菌株 (MRSA)。金黄色葡萄球菌的发病机制是由毒素的分泌推动的——例如破坏膜的成孔 α-毒素，其具有多种细胞靶点，包括上皮、内皮、白细胞和血小板。在这里，我们研究了使用人血小板膜包被的纳米粒子 (PNP) 作为仿生诱饵策略来中和金黄色葡萄球菌毒素并保持宿主细胞防御功能。PNPs 阻断了由以下因素引起的血小板损伤金黄色葡萄球菌分泌毒素，从而支持血小板活化和杀菌活性。同样，PNPs 阻断了由金黄色葡萄球菌分泌的毒素诱导的巨噬细胞损伤，从而支持巨噬细胞氧化爆发、一氧化氮产生和杀菌活性，并减少 MRSA 诱导的中性粒细胞胞外陷阱释放。在 MRSA 全身感染的小鼠模型中，PNP 给药减少了血液中的细菌数量并防止死亡。总之，目前工作的结果证明了 PNP 在毒素中和、细胞保护和增加宿主对侵袭性金黄色葡萄球菌感染的抵抗力方面的治疗益处。