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The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase

Author

Listed:
  • Bo Ma

    (Fourth Military Medical University)

  • Chao Fang

    (Fourth Military Medical University)

  • Linshan Lu

    (Fourth Military Medical University)

  • Mingzhi Wang

    (Fourth Military Medical University)

  • Xiaoyan Xue

    (Fourth Military Medical University)

  • Ying Zhou

    (Fourth Military Medical University)

  • Mingkai Li

    (Fourth Military Medical University)

  • Yue Hu

    (Fourth Military Medical University)

  • Xiaoxing Luo

    (Fourth Military Medical University)

  • Zheng Hou

    (Fourth Military Medical University)

Abstract

New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.

Suggested Citation

  • Bo Ma & Chao Fang & Linshan Lu & Mingzhi Wang & Xiaoyan Xue & Ying Zhou & Mingkai Li & Yue Hu & Xiaoxing Luo & Zheng Hou, 2019. "The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11503-3
    DOI: 10.1038/s41467-019-11503-3
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    Cited by:

    1. Zifan Ye & Lei Fu & Shuangyu Li & Ziying Chen & Jianhong Ouyang & Xinci Shang & Yanli Liu & Lianghui Gao & Yipeng Wang, 2024. "Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    2. Xiaojuan Wang & Xiaoling Xu & Shaojun Zhang & Na Chen & Yunfeng Sun & Kuifen Ma & Dongsheng Hong & Lu Li & Yongzhong Du & Xiaoyang Lu & Saiping Jiang, 2022. "TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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