Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome

Summary: Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used...

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Autores principales:	Kathy N. Lam, Peter Spanogiannopoulos, Paola Soto-Perez, Margaret Alexander, Matthew J. Nalley, Jordan E. Bisanz, Renuka R. Nayak, Allison M. Weakley, Feiqiao B. Yu, Peter J. Turnbaugh
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	human gut microbiome bacteriophage CRISPR-Cas systems microbiome editing genomic deletions strain-specific targeting Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3c9ce58edeae4b90b479eb9f6c0e4cb3
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spelling	oai:doaj.org-article:3c9ce58edeae4b90b479eb9f6c0e4cb32021-11-04T04:29:18ZPhage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome2211-124710.1016/j.celrep.2021.109930https://doaj.org/article/3c9ce58edeae4b90b479eb9f6c0e4cb32021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014030https://doaj.org/toc/2211-1247Summary: Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.Kathy N. LamPeter SpanogiannopoulosPaola Soto-PerezMargaret AlexanderMatthew J. NalleyJordan E. BisanzRenuka R. NayakAllison M. WeakleyFeiqiao B. YuPeter J. TurnbaughElsevierarticlehuman gut microbiomebacteriophageCRISPR-Cas systemsmicrobiome editinggenomic deletionsstrain-specific targetingBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109930- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human gut microbiome bacteriophage CRISPR-Cas systems microbiome editing genomic deletions strain-specific targeting Biology (General) QH301-705.5
spellingShingle	human gut microbiome bacteriophage CRISPR-Cas systems microbiome editing genomic deletions strain-specific targeting Biology (General) QH301-705.5 Kathy N. Lam Peter Spanogiannopoulos Paola Soto-Perez Margaret Alexander Matthew J. Nalley Jordan E. Bisanz Renuka R. Nayak Allison M. Weakley Feiqiao B. Yu Peter J. Turnbaugh Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
description	Summary: Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.
format	article
author	Kathy N. Lam Peter Spanogiannopoulos Paola Soto-Perez Margaret Alexander Matthew J. Nalley Jordan E. Bisanz Renuka R. Nayak Allison M. Weakley Feiqiao B. Yu Peter J. Turnbaugh
author_facet	Kathy N. Lam Peter Spanogiannopoulos Paola Soto-Perez Margaret Alexander Matthew J. Nalley Jordan E. Bisanz Renuka R. Nayak Allison M. Weakley Feiqiao B. Yu Peter J. Turnbaugh
author_sort	Kathy N. Lam
title	Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
title_short	Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
title_full	Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
title_fullStr	Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
title_full_unstemmed	Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome
title_sort	phage-delivered crispr-cas9 for strain-specific depletion and genomic deletions in the gut microbiome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3c9ce58edeae4b90b479eb9f6c0e4cb3
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Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome

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