Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization

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 hyperpo...

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Bibliographic Details
Main Authors: Nath Bhaumik Kaushik
Hetényi Anasztázia
Olajos Gábor
Martins Ana
Spohn Réka
Németh Lukács
Jójárt Balázs
Szili Petra
Dunai Anett
Jangir Pramod Kumar
Daruka Lejla
Földesi Imre
Kata Diána
Pál Csaba
Martinek Tamás
Format: Article
Published: 2022
Series:MOLECULAR SYSTEMS DESIGN & ENGINEERING 7 No. 1
Subjects:
doi:10.1039/D1ME00118C

mtmt:32493048
Online Access:http://publicatio.bibl.u-szeged.hu/24074
Description
Summary: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.
Physical Description:21-33
ISSN:2058-9689