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Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases
Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9(1, 2) delivered by a bacteriophage...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317352/ https://www.ncbi.nlm.nih.gov/pubmed/25282355 http://dx.doi.org/10.1038/nbt.3043 |
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author | Bikard, David Euler, Chad Jiang, Wenyan Nussenzweig, Philip M. Goldberg, Gregory W. Duportet, Xavier Fischetti, Vincent A. Marraffini, Luciano A. |
author_facet | Bikard, David Euler, Chad Jiang, Wenyan Nussenzweig, Philip M. Goldberg, Gregory W. Duportet, Xavier Fischetti, Vincent A. Marraffini, Luciano A. |
author_sort | Bikard, David |
collection | PubMed |
description | Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9(1, 2) delivered by a bacteriophage. We show that Cas9 re-programmed to target virulence genes kills virulent, but not avirulent, Staphylococcus aureus. Re-programming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes(3, 4) and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also demonstrate the approach in vivo, showing its efficacy against S. aureus in a mouse skin colonization model. This new technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner. |
format | Online Article Text |
id | pubmed-4317352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43173522015-05-01 Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases Bikard, David Euler, Chad Jiang, Wenyan Nussenzweig, Philip M. Goldberg, Gregory W. Duportet, Xavier Fischetti, Vincent A. Marraffini, Luciano A. Nat Biotechnol Article Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9(1, 2) delivered by a bacteriophage. We show that Cas9 re-programmed to target virulence genes kills virulent, but not avirulent, Staphylococcus aureus. Re-programming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes(3, 4) and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also demonstrate the approach in vivo, showing its efficacy against S. aureus in a mouse skin colonization model. This new technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner. 2014-10-05 2014-11 /pmc/articles/PMC4317352/ /pubmed/25282355 http://dx.doi.org/10.1038/nbt.3043 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Bikard, David Euler, Chad Jiang, Wenyan Nussenzweig, Philip M. Goldberg, Gregory W. Duportet, Xavier Fischetti, Vincent A. Marraffini, Luciano A. Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title | Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title_full | Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title_fullStr | Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title_full_unstemmed | Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title_short | Development of sequence-specific antimicrobials based on programmable CRISPR-Cas nucleases |
title_sort | development of sequence-specific antimicrobials based on programmable crispr-cas nucleases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317352/ https://www.ncbi.nlm.nih.gov/pubmed/25282355 http://dx.doi.org/10.1038/nbt.3043 |
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