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Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens

Author

Listed:
  • Rui Wang

    (Chinese Academy of Sciences
    Chengdu Medical College)

  • Xian Shu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Huiwei Zhao

    (Chinese Academy of Sciences)

  • Qiong Xue

    (Chinese Academy of Sciences)

  • Chao Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Aici Wu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Feiyue Cheng

    (Chinese Academy of Sciences)

  • Lingyun Wang

    (Chinese Academy of Sciences
    Shandong Agricultural University)

  • Yihan Zhang

    (Chinese Academy of Sciences
    Hebei University)

  • Jie Feng

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Nannan Wu

    (Shanghai Public Health Clinical Center, Fudan University)

  • Ming Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to ‘ATTACK’ MDR pathogens.

Suggested Citation

  • Rui Wang & Xian Shu & Huiwei Zhao & Qiong Xue & Chao Liu & Aici Wu & Feiyue Cheng & Lingyun Wang & Yihan Zhang & Jie Feng & Nannan Wu & Ming Li, 2023. "Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37789-y
    DOI: 10.1038/s41467-023-37789-y
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    References listed on IDEAS

    as
    1. Blake Wiedenheft & Samuel H. Sternberg & Jennifer A. Doudna, 2012. "RNA-guided genetic silencing systems in bacteria and archaea," Nature, Nature, vol. 482(7385), pages 331-338, February.
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