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

作者：Bo Ma, Chao Fang, Lin-Shan Lu, Mingzhi Wang, Xiaoyan Xue, Ying Zhou, Mingkai Li, Yue Hu, Xiaoxing Luo, Zheng Hou · 发表于：Nature Communications · 年份：2019 · DOI：10.1038/s41467-019-11503-3 · 被引用次数：181 · 研究领域：Antibiotic Resistance in Bacteria、Bacterial biofilms and quorum sensing、Antibiotic Use and Resistance

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.