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

• DOI: 10.1039/d4sm00220b
• Publication Date: 2024-04-29T06:02:13Z
• Authors: Saheli Mitra; Bhairavi Chanders...; Yunshu Li; Mark Coopershlyak; Margot E. Mahoney; Brandt Evans; Rachel Koenig; Stephen C. L. Hall; Beate Klösgen; Frank Heinrich; Berthony Deslouches; Stephanie Tristra...
• Keywords: Small-angle X-ray scattering

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 shorter exhibits greater bactericidal activity against both Gram-negative (G(-)) Gram-positive (G(+)) bacteria. Remarkably, AMPs are non-toxic eukaryotic cells. The heightened effectiveness is attributed its increased hydrophobicity (H) compared LE-55. Circular dichroism (CD) reveals adopt β-sheet random coil structures in lipid model membranes (LMMs) mimicking G(-) G(+) bacteria, so secondary structure not cause potency difference. X-ray diffuse scattering (XDS) chain order LE-53, a potential key distinction. Additionally, XDS study uncovers significant link between LE-53's upper hydrocarbon location LMMs efficacy. Neutron reflectometry (NR) confirms AMP locations determined using XDS. Solution small angle (SAXS) demonstrates ability induce vesicle fusion bacterial without affecting LMMs, offering promising strategy combat antibiotic-resistant strains while preserving human cell integrity, whereas has smaller fusion.