Immunomimetic Designer Cells Protect Mice from MRSA Infection

• Ying Liu ^[1] ; Peng Bai ^[1] ; Anne-Kathrin Woischnig ^[2]
  1. [1] Swiss Federal Institute of Technology in Zurich

     Swiss Federal Institute of Technology in Zurich

     Zürich, Suiza

     
  2. [2] Department of Biomedicine, University Hospital Basel
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 2, 2018, págs. 259-270
• Idioma: inglés
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• Resumen

  • 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.