Engineered phage with antibacterial CRISPR-Cas selectively reduce E. coli burden in mice.

Journal

Nature biotechnology

ISSN: 1546-1696

Titre abrégé: Nat Biotechnol

Pays: United States

ID NLM: 9604648

Informations de publication

Date de publication:
04 May 2023

Historique:

received: 31 05 2022

accepted: 22 03 2023

pubmed: 5 5 2023

medline: 5 5 2023

entrez: 4 5 2023

Statut: aheadofprint

Résumé

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR-Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients.

Identifiants

DOI: 10.1038/s41587-023-01759-y PMID: 37142704

pubmed: 37142704

doi: 10.1038/s41587-023-01759-y

pii: 10.1038/s41587-023-01759-y

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Commentaires et corrections

Type : CommentIn

Informations de copyright

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