High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing

Abstract Antibiotic resistance threatens our ability to treat infectious diseases, spurring interest in alternative antimicrobial technologies. The use of bacterial conjugation to deliver CRISPR‐cas systems programmed to precisely eliminate antibiotic‐resistant bacteria represents a promising approa...

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Autores principales:	Kevin Neil, Nancy Allard, Patricia Roy, Frédéric Grenier, Alfredo Menendez, Vincent Burrus, Sébastien Rodrigue
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	antibiotic resistance antimicrobials bacterial conjugation CRISPR‐Cas9 synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c9ddf6574182493ea5f2edf2a1f7117a
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spelling	oai:doaj.org-article:c9ddf6574182493ea5f2edf2a1f7117a2021-11-11T11:30:47ZHigh‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing1744-429210.15252/msb.202110335https://doaj.org/article/c9ddf6574182493ea5f2edf2a1f7117a2021-10-01T00:00:00Zhttps://doi.org/10.15252/msb.202110335https://doaj.org/toc/1744-4292Abstract Antibiotic resistance threatens our ability to treat infectious diseases, spurring interest in alternative antimicrobial technologies. The use of bacterial conjugation to deliver CRISPR‐cas systems programmed to precisely eliminate antibiotic‐resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. We have optimized the transfer efficiency of conjugative plasmid TP114 using accelerated laboratory evolution. We hence generated a potent conjugative delivery vehicle for CRISPR‐cas9 that can eliminate > 99.9% of targeted antibiotic‐resistant Escherichia coli in the mouse gut microbiota using a single dose. We then applied this system to a Citrobacter rodentium infection model, achieving full clearance within four consecutive days of treatment.Kevin NeilNancy AllardPatricia RoyFrédéric GrenierAlfredo MenendezVincent BurrusSébastien RodrigueWileyarticleantibiotic resistanceantimicrobialsbacterial conjugationCRISPR‐Cas9synthetic biologyBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance antimicrobials bacterial conjugation CRISPR‐Cas9 synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	antibiotic resistance antimicrobials bacterial conjugation CRISPR‐Cas9 synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920 Kevin Neil Nancy Allard Patricia Roy Frédéric Grenier Alfredo Menendez Vincent Burrus Sébastien Rodrigue High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
description	Abstract Antibiotic resistance threatens our ability to treat infectious diseases, spurring interest in alternative antimicrobial technologies. The use of bacterial conjugation to deliver CRISPR‐cas systems programmed to precisely eliminate antibiotic‐resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. We have optimized the transfer efficiency of conjugative plasmid TP114 using accelerated laboratory evolution. We hence generated a potent conjugative delivery vehicle for CRISPR‐cas9 that can eliminate > 99.9% of targeted antibiotic‐resistant Escherichia coli in the mouse gut microbiota using a single dose. We then applied this system to a Citrobacter rodentium infection model, achieving full clearance within four consecutive days of treatment.
format	article
author	Kevin Neil Nancy Allard Patricia Roy Frédéric Grenier Alfredo Menendez Vincent Burrus Sébastien Rodrigue
author_facet	Kevin Neil Nancy Allard Patricia Roy Frédéric Grenier Alfredo Menendez Vincent Burrus Sébastien Rodrigue
author_sort	Kevin Neil
title	High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title_short	High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title_full	High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title_fullStr	High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title_full_unstemmed	High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title_sort	high‐efficiency delivery of crispr‐cas9 by engineered probiotics enables precise microbiome editing
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c9ddf6574182493ea5f2edf2a1f7117a
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High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing

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