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A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus

Author

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  • J. Andrés Valderrama

    (University of California, San Diego
    University of California, San Diego)

  • Surashree S. Kulkarni

    (University of California, San Diego
    University of California, San Diego)

  • Victor Nizet

    (University of California, San Diego
    University of California, San Diego
    University of California, San Diego)

  • Ethan Bier

    (University of California, San Diego
    University of California, San Diego)

Abstract

Gene-drive systems in diploid organisms bias the inheritance of one allele over another. CRISPR-based gene-drive expresses a guide RNA (gRNA) into the genome at the site where the gRNA directs Cas9-mediated cleavage. In the presence of Cas9, the gRNA cassette and any linked cargo sequences are copied via homology-directed repair (HDR) onto the homologous chromosome. Here, we develop an analogous CRISPR-based gene-drive system for the bacterium Escherichia coli that efficiently copies a gRNA cassette and adjacent cargo flanked with sequences homologous to the targeted gRNA/Cas9 cleavage site. This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with ~ 100-fold greater efficiency than control CRISPR-based methods, suggesting an amplifying positive feedback loop due to increasing gRNA dosage. Pro-AG can likewise effectively edit large plasmids or single-copy genomic targets or introduce functional genes, foreshadowing potential applications to biotechnology or biomedicine.

Suggested Citation

  • J. Andrés Valderrama & Surashree S. Kulkarni & Victor Nizet & Ethan Bier, 2019. "A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13649-6
    DOI: 10.1038/s41467-019-13649-6
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    Cited by:

    1. Sara Sanz Juste & Emily M. Okamoto & Christina Nguyen & Xuechun Feng & Víctor López Del Amo, 2023. "Next-generation CRISPR gene-drive systems using Cas12a nuclease," Nature Communications, Nature, vol. 14(1), pages 1-8, December.

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