2. Academic Validation
  3. The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase

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

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.

Figures
Products