Issue 20, 2024

Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes

Abstract

This research addresses the growing menace of antibiotic resistance by exploring antimicrobial peptides (AMPs) as alternatives to conventional antibiotics. Specifically, we investigate two linear amphipathic AMPs, LE-53 (12-mer) and LE-55 (16-mer), finding that the shorter LE-53 exhibits greater bactericidal activity against both Gram-negative (G(−)) and Gram-positive (G(+)) bacteria. Remarkably, both AMPs are non-toxic to eukaryotic cells. The heightened effectiveness of LE-53 is attributed to its increased hydrophobicity (H) compared to LE-55. Circular dichroism (CD) reveals that LE-53 and LE-55 both adopt β-sheet and random coil structures in lipid model membranes (LMMs) mimicking G(−) and G(+) bacteria, so secondary structure is not the cause of the potency difference. X-ray diffuse scattering (XDS) reveals increased lipid chain order in LE-53, a potential key distinction. Additionally, XDS study uncovers a significant link between LE-53's upper hydrocarbon location in G(−) and G(+) LMMs and its efficacy. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Solution small angle X-ray scattering (SAXS) demonstrates LE-53's ability to induce vesicle fusion in bacterial LMMs without affecting eukaryotic LMMs, offering a promising strategy to combat antibiotic-resistant strains while preserving human cell integrity, whereas LE-55 has a smaller ability to induce fusion.

Graphical abstract: Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes

Supplementary files

Article information

Article type
Paper
Submitted
16 Feb 2024
Accepted
26 Apr 2024
First published
29 Apr 2024
This article is Open Access
Creative Commons BY license

Soft Matter, 2024,20, 4088-4101

Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes

S. Mitra, B. Chandersekhar, Y. Li, M. Coopershlyak, M. E. Mahoney, B. Evans, R. Koenig, S. C. L. Hall, B. Klösgen, F. Heinrich, B. Deslouches and S. Tristram-Nagle, Soft Matter, 2024, 20, 4088 DOI: 10.1039/D4SM00220B

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