期刊
MOLECULAR SYSTEMS DESIGN & ENGINEERING
卷 7, 期 1, 页码 21-33出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1me00118c
关键词
-
类别
资金
- European Research Council [H2020-ERC-2014-CoG 648364, H2020-ERC-2019-PoC 862077]
- ELKH Lendulet Programme [LP-2017-10/2020]
- National Research, Development and Innovation Office, Hungary [KKP 126506]
- National Laboratory of Biotechnology Grant [NKFIH-871-3/2020, GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020]
- NKFI [PD 116222, K134754]
- Ministry of Human Capacities, Hungary [20391-3/2018/FEKUSTRAT]
The novel PGLa analogues induce sustained membrane hyperpolarization and significantly reduce antibiotic resistance of multi-drug resistant bacteria. This antibiotic potentiation is mediated by altering cellular ion transport and manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance.
The negative membrane potential of bacterial cells influences crucial cellular processes. Inspired by the molecular scaffold of the antimicrobial peptide PGLa, we have developed antimicrobial foldamers with a computer-guided design strategy. The novel PGLa analogues induce sustained membrane hyperpolarization. When co-administered as an adjuvant, the resulting compounds - PGLb1 and PGLb2 - have substantially reduced the level of antibiotic resistance of multi-drug resistant Escherichia coli, Klebsiella pneumoniae and Shigella flexneri clinical isolates. The observed antibiotic potentiation was mediated by hyperpolarization of the bacterial membrane caused by the alteration of cellular ion transport. Specifically, PGLb1 and PGLb2 are selective ionophores that enhance the Goldman-Hodgkin-Katz potential across the bacterial membrane. These findings indicate that manipulating bacterial membrane electrophysiology could be a valuable tool to overcome antimicrobial resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据