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

Nature Communications
Bo MaZheng Hou

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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Citations

Sep 10, 2019·Protein Science : a Publication of the Protein Society·Simon Booth, Richard J Lewis
Sep 17, 2020·Biophysics Reviews·Pallavi KumariAntonio Benedetto
Feb 6, 2020·Chemical Communications : Chem Comm·Cheng ChenLe-Yun Sun
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Methods Mentioned

BETA
scanning electron microscopy
bronchoalveolar lavage
isothermal titration calorimetry
microscale thermophoresis
nuclear magnetic resonance
protein assay
ELISA

Software Mentioned

ImageJ
Origin

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