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...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2022
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| Sorozat: | MOLECULAR SYSTEMS DESIGN & ENGINEERING
7 No. 1 |
| Tárgyszavak: | |
| doi: | 10.1039/D1ME00118C |
| mtmt: | 32493048 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/24074 |
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| 520 | 3 | |a 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. | |
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| 700 | 0 | 1 | |a Spohn Réka |e aut |
| 700 | 0 | 1 | |a Németh Lukács |e aut |
| 700 | 0 | 1 | |a Jójárt Balázs |e aut |
| 700 | 0 | 1 | |a Szili Petra |e aut |
| 700 | 0 | 1 | |a Dunai Anett |e aut |
| 700 | 0 | 1 | |a Jangir Pramod Kumar |e aut |
| 700 | 0 | 1 | |a Daruka Lejla |e aut |
| 700 | 0 | 1 | |a Földesi Imre |e aut |
| 700 | 0 | 1 | |a Kata Diána |e aut |
| 700 | 0 | 1 | |a Pál Csaba |e aut |
| 700 | 0 | 1 | |a Martinek Tamás |e aut |
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