{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T05:04:30Z","timestamp":1779771870128,"version":"3.53.1"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research Projects of Higher Education Institutions in Henan Province","award":["26A550026"],"award-info":[{"award-number":["26A550026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The overuse of traditional antimicrobial agents has accelerated the global spread of drug-resistant bacteria, posing a severe threat to global public health. Methods: In this work, a series of lipopeptides with varying fatty acid chain lengths were designed using the targeting antimicrobial peptide CL5 as the parental peptide. A variety of technical methods, including spectroscopic techniques, electron microscopy and computer simulation, were adopted to explore the self-assembly properties of the lipopeptides and their antimicrobial properties against Gram-positive and Gram-negative bacteria. Results: The results showed that lipopeptide self-assembly could be triggered by fatty acid chain modification with a carbon chain length exceeding 8 atoms, and hydrophobic interactions between fatty acid chains were the primary driving force for this process. The geometric mean of the minimum inhibitory concentrations of the lipopeptides exhibited an approximate \u201cU\u201d-shaped correlation with the length of the fatty acid chains. Among these lipopeptides, C8CL5\u2013C12CL5 exhibited broad-spectrum and highly potent antimicrobial activity, with geometric means of 6.20, 5.16, and 8.00 \u03bcM against all tested bacteria, and selectivity index values of 12.26, 8.14, and 7.48, respectively. Furthermore, the lipopeptides exhibited high selectivity, rapid time-killing kinetics, as well as excellent thermal, pH and salt stability. Mechanistic studies revealed that the lipopeptides exerted antimicrobial effects through multiple pathways: disrupted bacterial cell membranes and caused the leakage of cellular contents, bound to bacterial genomic DNA, and promoted the production of reactive oxygen species. Conclusions: Collectively, lipopeptides modified with appropriate fatty acid chains exhibit broad-spectrum and highly effective antimicrobial activity, making them promising alternatives to traditional antibiotics for the treatment of bacterial infections.<\/jats:p>","DOI":"10.3390\/antibiotics15050518","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:34Z","timestamp":1779291934000},"page":"518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Fatty Acid Chain Modification on the Self-Assembly Behavior and Antimicrobial Activity of Antimicrobial Peptides"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-5494","authenticated-orcid":false,"given":"Hongyan","family":"Yang","sequence":"first","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqian","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutao","family":"Min","sequence":"additional","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics Department, R&D Center, Autobio Diagnostics Co., Ltd., Zhengzhou 450016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchao","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-1238","authenticated-orcid":false,"given":"Fei","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Resource Insects, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Food and Health Engineering, Zhengzhou University of Technology, Zhengzhou 450044, China"},{"name":"College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5851\/kosfa.2020.e75","article-title":"Etiological Agents Implicated in Foodborne Illness World Wide","volume":"41","author":"Lee","year":"2021","journal-title":"Food Sci. 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