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

  • Nat Commun. 2019 Aug 6;10(1):3517. doi: 10.1038/s41467-019-11503-3.
Bo Ma  1 ,  Chao Fang  1 ,  Linshan Lu  2 ,  Mingzhi Wang  1 ,  Xiaoyan Xue  1 ,  Ying Zhou  1 ,  Mingkai Li  1 ,  Yue Hu  1 ,  Xiaoxing Luo  3 ,  Zheng Hou  4
Affiliations
  • 1. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • 2. Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
  • 3. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
  • 4. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
PMID: 31388008 DOI: 10.1038/s41467-019-11503-3
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.

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