Immunomimetic Designer Cells Protect Mice from MRSA Infection.

Authors:
Ying Liu
Ying Liu
School of Pharmacy
Madison | United States
Peng Bai
Peng Bai
West China School of Preclinical and Forensic Medicine
China
Ghislaine Charpin-El Hamri
Ghislaine Charpin-El Hamri
Institut Universitaire de Technologie
France
Haifeng Ye
Haifeng Ye
East China Normal University
China
Marc Folcher
Marc Folcher
University of Basel
Switzerland
Mingqi Xie
Mingqi Xie
Department of Biosystems Science and Engineering
Nina Khanna
Nina Khanna
University Hospital Basel
Switzerland

Cell 2018 Jul 21;174(2):259-270.e11. Epub 2018 Jun 21.

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Faculty of Science, University of Basel, 4031 Basel, Switzerland. Electronic address:

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.

Abstract Video

Designer Cells as MRSA Assassins / Cell, July 12 , 2018 (Vol. 174, Issue 2)


Source: Cell Press

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Source
http://dx.doi.org/10.1016/j.cell.2018.05.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057273PMC

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July 2018
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