{"doi":"10.1039/d4sm00220b","title":"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.","journal":"Soft Matter","year":2024,"id":442363,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1107941,"name":"Bhairavi Chandersekhar","orcid":null,"position":1,"is_corresponding":false},{"id":807407,"name":"Yunshu Li","orcid":null,"position":2,"is_corresponding":false},{"id":1107940,"name":"Mark Coopershlyak","orcid":null,"position":3,"is_corresponding":false},{"id":1256156,"name":"Margot E. Mahoney","orcid":null,"position":4,"is_corresponding":false},{"id":1107944,"name":"Brandt Evans","orcid":null,"position":5,"is_corresponding":false},{"id":1107942,"name":"Rachel Koenig","orcid":null,"position":6,"is_corresponding":false},{"id":1255813,"name":"Stephen C. L. Hall","orcid":"0000-0003-0753-5123","position":7,"is_corresponding":false},{"id":1255814,"name":"Beate Klösgen","orcid":"0000-0002-2334-0388","position":8,"is_corresponding":false},{"id":346067,"name":"Frank Heinrich","orcid":"0000-0002-8579-553X","position":9,"is_corresponding":false},{"id":264224,"name":"Berthony Deslouches","orcid":"0000-0003-4797-7065","position":10,"is_corresponding":false},{"id":402407,"name":"Stephanie Tristram‐Nagle","orcid":"0000-0003-2271-7056","position":11,"is_corresponding":false},{"id":1107545,"name":"Saheli Mitra","orcid":"0000-0002-5132-3526","position":0,"is_corresponding":true}],"reference_count":135,"raw_metadata":null,"created_at":"2026-07-19T02:01:15.932178Z","pmid":"38712559","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}