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Systematic strategies for developing phage resistant Escherichia coli strains

Author

Listed:
  • Xuan Zou

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Xiaohong Xiao

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Ziran Mo

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University
    the First Affiliated Hospital of Shenzhen University)

  • Yashi Ge

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Xing Jiang

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University
    the First Affiliated Hospital of Shenzhen University)

  • Ruolin Huang

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University
    the First Affiliated Hospital of Shenzhen University)

  • Mengxue Li

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Zixin Deng

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Shi Chen

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University
    the First Affiliated Hospital of Shenzhen University)

  • Lianrong Wang

    (Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University)

  • Sang Yup Lee

    (Korea Advanced Institute of Science and Technology)

Abstract

Phages are regarded as powerful antagonists of bacteria, especially in industrial fermentation processes involving bacteria. While bacteria have developed various defense mechanisms, most of which are effective against a narrow range of phages and consequently exert limited protection from phage infection. Here, we report a strategy for developing phage-resistant Escherichia coli strains through the simultaneous genomic integration of a DNA phosphorothioation-based Ssp defense module and mutations of components essential for the phage life cycle. The engineered E. coli strains show strong resistance against diverse phages tested without affecting cell growth. Additionally, the resultant engineered phage-resistant strains maintain the capabilities of producing example recombinant proteins, D-amino acid oxidase and coronavirus-encoded nonstructural protein nsp8, even under high levels of phage cocktail challenge. The strategy reported here will be useful for developing engineered E. coli strains with improved phage resistance for various industrial fermentation processes for producing recombinant proteins and chemicals of interest.

Suggested Citation

  • Xuan Zou & Xiaohong Xiao & Ziran Mo & Yashi Ge & Xing Jiang & Ruolin Huang & Mengxue Li & Zixin Deng & Shi Chen & Lianrong Wang & Sang Yup Lee, 2022. "Systematic strategies for developing phage resistant Escherichia coli strains," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31934-9
    DOI: 10.1038/s41467-022-31934-9
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    References listed on IDEAS

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    1. Lei Xiong & Siyi Liu & Si Chen & Yao Xiao & Bochen Zhu & Yali Gao & Yujing Zhang & Beibei Chen & Jie Luo & Zixin Deng & Xiangdong Chen & Lianrong Wang & Shi Chen, 2019. "A new type of DNA phosphorothioation-based antiviral system in archaea," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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    1. Haiyan Gao & Xinqi Gong & Jinchuan Zhou & Yubing Zhang & Jinsong Duan & Yue Wei & Liuqing Chen & Zixin Deng & Jiawei Wang & Shi Chen & Geng Wu & Lianrong Wang, 2022. "Nicking mechanism underlying the DNA phosphorothioate-sensing antiphage defense by SspE," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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