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

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 re...

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Detalles Bibliográficos
Autores principales: Neil, Kevin, Allard, Nancy, Roy, Patricia, Grenier, Frédéric, Menendez, Alfredo, Burrus, Vincent, Rodrigue, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527022/
https://www.ncbi.nlm.nih.gov/pubmed/34665940
http://dx.doi.org/10.15252/msb.202110335
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author Neil, Kevin
Allard, Nancy
Roy, Patricia
Grenier, Frédéric
Menendez, Alfredo
Burrus, Vincent
Rodrigue, Sébastien
author_facet Neil, Kevin
Allard, Nancy
Roy, Patricia
Grenier, Frédéric
Menendez, Alfredo
Burrus, Vincent
Rodrigue, Sébastien
author_sort Neil, Kevin
collection PubMed
description 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.
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spelling pubmed-85270222021-10-29 High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing Neil, Kevin Allard, Nancy Roy, Patricia Grenier, Frédéric Menendez, Alfredo Burrus, Vincent Rodrigue, Sébastien Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2021-10-19 /pmc/articles/PMC8527022/ /pubmed/34665940 http://dx.doi.org/10.15252/msb.202110335 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Neil, Kevin
Allard, Nancy
Roy, Patricia
Grenier, Frédéric
Menendez, Alfredo
Burrus, Vincent
Rodrigue, Sébastien
High‐efficiency delivery of CRISPR‐Cas9 by engineered probiotics enables precise microbiome editing
title 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_short 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
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527022/
https://www.ncbi.nlm.nih.gov/pubmed/34665940
http://dx.doi.org/10.15252/msb.202110335
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