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Emslander, Q.* ; Vogele, K.* ; Braun, P.* ; Stender, J.* ; Willy, C.* ; Joppich, M.* ; Hammerl, J.A.* ; Abele, M.* ; Meng, C.* ; Pichlmair, A.* ; Ludwig, C.* ; Bugert, J.J.* ; Simmel, F.C.* ; Westmeyer, G.G.

Cell-free production of personalized therapeutic phages targeting multidrug-resistant bacteria.

Cell Chem. Bio. 29, 1434-1445.e7 (2022)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Bacteriophages are potent therapeutics against biohazardous bacteria, which rapidly develop multidrug resistance. However, routine administration of phage therapy is hampered by a lack of rapid production, safe bioengineering, and detailed characterization of phages. Thus, we demonstrate a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. Using mass spectrometry, we validated hypothetical and non-structural proteins and could also monitor the protein expression during phage assembly. Notably, a few microliters of a one-pot reaction produced effective doses of phages against enteroaggregative Escherichia coli (EAEC), Yersinia pestis, and Klebsiella pneumoniae. By co-expressing suitable host factors, we could extend the range of cell-free production to phages targeting gram-positive bacteria. We further introduce a non-genomic phage engineering method, which adds functionalities for only one replication cycle. In summary, we expect this cell-free methodology to foster reverse and forward phage engineering and customized production of clinical-grade bacteriophages.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Biosafety ; Cell-free Production ; Multidrug-resistant Bacteria ; Non-genomic Phage Engineering ; Non-structural Phage Proteins ; Personalized Medicine ; Phage Therapy ; Therapeutic Bacteriophages ; Time-resolved Proteomics
ISSN (print) / ISBN 2451-9448
e-ISSN 2451-9456
Zeitschrift Cell Chemical Biology
Quellenangaben Band: 29, Heft: 9, Seiten: 1434-1445.e7 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Massachusetts
Begutachtungsstatus Peer reviewed
Institut(e) Insitute of Synthetic Biomedicine (ISBM)
Förderungen Technische Universität München
Institut Pasteur
Deutsche Forschungsgemeinschaft
Shanmuga Sozhamannan
Laboratory for Molecular and Cellular Technology
JPEO
Federal Ministry of Economy and Climate Action
Defense Biological Product Assurance Office
CBRND-EB
Bavarian Ministry for Science