{"doi":"10.1021/acsomega.5c07162","title":"Dual Mechanisms of Action of a Halogenated Allyl Fatty Acid against Methicillin-Resistant <i>Staphylococcus aureus</i>","abstract":"High Resolution Image Download MS PowerPoint Slide Antimicrobial resistance in MRSA demands agents with new mechanisms. We evaluated two synthetic unsaturated fatty acids, 2-hexadecynoic acid (2-HDA) and ( Z )-2-allyl-3-bromo-2-hexadecenoic acid (DAT-51), across clinical and reference MRSA strains. Both compounds reduced the viability in a dose-dependent manner. Fluorescence microscopy and nucleic acid leakage demonstrated rapid membrane permeabilization; flow cytometry revealed strong depolarization, and SEM showed surface lesions consistent with pore formation. DAT-51 additionally induced Lipid II accumulation and inhibited MurA, whereas lipidomics indicated the selective incorporation of 2-HDA into bacterial phospholipids. Vero-cell assays showed a low cytotoxicity at concentrations exceeding MICs. Together, the data support a dual-action paradigm: 2-HDA primarily disrupts membranes via insertion and pore formation, while DAT-51 combines moderate membrane perturbation with the inhibition of peptidoglycan biosynthesis. These findings define complementary mechanisms for uFA-based agents and identify 2-HDA and DAT-51 as promising scaffolds against drug-resistant Gram-positive pathogens.","journal":"ACS Omega","year":2025,"id":548486,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":617175,"name":"Giancarlo Casillas-Vargas","orcid":null,"position":1,"is_corresponding":false},{"id":1442180,"name":"Karama Shayeb","orcid":null,"position":2,"is_corresponding":false},{"id":1442181,"name":"Alexis Rosado-Ortíz","orcid":null,"position":3,"is_corresponding":false},{"id":1442182,"name":"Luzmarie Reyes-Vicente","orcid":null,"position":4,"is_corresponding":false},{"id":1442183,"name":"Mayerli De Jesús-Vega","orcid":null,"position":5,"is_corresponding":false},{"id":1442184,"name":"Derik Amely-Gavilán","orcid":null,"position":6,"is_corresponding":false},{"id":1442185,"name":"Natasha Díaz-Cruz","orcid":null,"position":7,"is_corresponding":false},{"id":1442186,"name":"Gil Cortés-Rodríguez","orcid":null,"position":8,"is_corresponding":false},{"id":1442187,"name":"Jessica Said","orcid":null,"position":9,"is_corresponding":false},{"id":1442188,"name":"Jasmin Ceja-Vega","orcid":null,"position":10,"is_corresponding":false},{"id":1096707,"name":"Elizabeth Andersen","orcid":"0000-0001-9226-6479","position":11,"is_corresponding":false},{"id":1442189,"name":"Amani Rabadi","orcid":null,"position":12,"is_corresponding":false},{"id":1442190,"name":"Antonio Colom","orcid":null,"position":13,"is_corresponding":false},{"id":1441666,"name":"Harry Rivera","orcid":"0000-0002-4676-7114","position":14,"is_corresponding":false},{"id":1441667,"name":"Sunghee Lee","orcid":"0000-0003-2481-7982","position":15,"is_corresponding":false},{"id":453676,"name":"Nataliya Chorna","orcid":"0000-0002-7761-6802","position":16,"is_corresponding":false},{"id":340913,"name":"Kathleen M. Brundage","orcid":null,"position":17,"is_corresponding":false},{"id":501700,"name":"Néstor M. Carballeira","orcid":"0000-0001-7404-0505","position":18,"is_corresponding":false},{"id":501699,"name":"David J. Sanabria‐Ríos","orcid":"0000-0001-8797-1210","position":19,"is_corresponding":false},{"id":1442179,"name":"Jazmar Villarini-Torres","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41322630","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":[]}