Engineered Biomimetic Platelet Membrane-Coated Nanoparticles Block Staphylococcus aureus Cytotoxicity and Protect Against Lethal Systemic Infection

Engineering

Liangfang Zhang¹  Hua Gong²  Alexandra Stream³  Satoshi Uchiyama⁴  Victor Nizet⁵  Jwa-Kyung Kim⁶ 

[1] Corresponding authors.;Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea;Division of Host–Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA;Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea;Division of Host–Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA;;Division of Nephrology, Department of Internal Medicine &

关键词: Nanoparticle;    Nanosponge;    Platelet;    Staphylococcus aureus;    Bacterial toxins;    Sepsis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown