生物
溶葡萄球菌酶
金黄色葡萄球菌
微生物学
抗生素
生物膜
耐甲氧西林金黄色葡萄球菌
葡萄球菌感染
噬菌体疗法
万古霉素
基因
病毒学
细菌
噬菌体
大肠杆菌
遗传学
生物化学
作者
Ying Liu,Peng Bai,Anne-Kathrin Woischnig,Ghislaine Charpin‐El Hamri,Haifeng Ye,Marc Folcher,Mingqi Xie,Nina Khanna,Martin Fussenegger
出处
期刊:Cell
[Elsevier]
日期:2018-07-01
卷期号:174 (2): 259-270.e11
被引量:54
标识
DOI:10.1016/j.cell.2018.05.039
摘要
Summary
Many community- and hospital-acquired bacterial infections are caused by antibiotic-resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) predisposes humans to invasive infections that are difficult to eradicate. We designed a closed-loop gene network programming mammalian cells to autonomously detect and eliminate bacterial infections. The genetic circuit contains human Toll-like receptors as the bacterial sensor and a synthetic promoter driving reversible and adjustable expression of lysostaphin, a bacteriolytic enzyme highly lethal to S. aureus. Immunomimetic designer cells harboring this genetic circuit exhibited fast and robust sense-and-destroy kinetics against live staphylococci. When tested in a foreign-body infection model in mice, microencapsulated cell implants prevented planktonic MRSA infection and reduced MRSA biofilm formation by 91%. Notably, this system achieved a 100% cure rate of acute MRSA infections, whereas conventional vancomycin treatment failed. These results suggest that immunomimetic designer cells could offer a therapeutic approach for early detection, prevention, and cure of pathogenic infections in the post-antibiotic era. Video Abstract
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