Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials

David Bikard 1 Chad Euler 2 Wenyan Jiang 1 Nussenzweig Philip 1 Gregory Goldberg 1 Xavier Duportet 3, 4 Vincent Fischetti 2 Luciano Marraffini 1
1 Laboratory of Bacteriology
2 Laboratory of Bacterial Pathogenesis and Immunology
3 BE - Department of Biological Engineering [Cambridge]
4 Lifeware - Computational systems biology and optimization
Inria Paris-Rocquencourt
Abstract : 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 (refs.1,2) delivered by a bacteriophage. We show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. Reprogramming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also show that CRISPR-Cas9 antimicrobials function in vivo to kill S. aureus in a mouse skin colonization model. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.
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Nature Biotechnology, Nature Publishing Group, 2014, 32 (11), pp.5. 〈10.1038/nbt.3043〉
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https://hal.archives-ouvertes.fr/hal-01103559
Contributeur : Gregory Batt <>
Soumis le : jeudi 15 janvier 2015 - 01:29:06
Dernière modification le : vendredi 2 novembre 2018 - 15:20:04

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David Bikard, Chad Euler, Wenyan Jiang, Nussenzweig Philip, Gregory Goldberg, et al.. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nature Biotechnology, Nature Publishing Group, 2014, 32 (11), pp.5. 〈10.1038/nbt.3043〉. 〈hal-01103559〉

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