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However, antibiotic misuse has led to drug resistance, which now constitutes a serious health problem. In this context, antimicrobial peptides (AMPs) constitute a natural group of short proteins, varying in structure and length, that act against certain types of bacterial pathogens. The antimicrobial peptide 1018-K6 (VRLIVKVRIWRR- NH2) has significant bactericidal and antibiofilm activity against Listeria monocytogenes isolates, and against different strains and serotypes of Salmonella. Here, the mechanism of action of 1018-K6 was explored further to understand the peptide\u2013membrane interactions relevant to its activity, and to define their determinants. We combined studies with model synthetic membranes (liposomes) and model biological membranes, assessing the absorption maximum and the quenching of 1018-K6 fluorescence in aqueous and lipid environments, the self-quenching of carboxyfluorescein, as well as performing lipid sedimentation assays. The data obtained reflect the differential interactions of the 1018-K6 peptide with eukaryotic and prokaryotic membranes, and the specific interactions and mechanisms of action in the three prokaryotic species studied: Salmonella Typhimurium2GN, Escherichia coli3GN, and Staphylococcus aureus3GP. The AMP 1018-K6 is a candidate to prevent (food preservation) or treat (antibiotic use) infections caused by certain pathogenic bacteria, especially some that are resistant to current antibiotics.<\/jats:p>","DOI":"10.3390\/ijms232012392","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"12392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Antimicrobial Peptide 1018-K6 Interacts Distinctly with Eukaryotic and Bacterial Membranes, the Basis of Its Specificity and Bactericidal Activity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4413-142X","authenticated-orcid":false,"given":"Rosa Luisa","family":"Ambrosio","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, Unit of Food Hygiene, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-607X","authenticated-orcid":false,"given":"Catalina Ana","family":"Rossell\u00f3","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Laminar Pharmaceuticals, 07121 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2314-3026","authenticated-orcid":false,"given":"Doralicia","family":"Casares","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Laminar Pharmaceuticals, 07121 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-4075","authenticated-orcid":false,"given":"Gianna","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and BioResources, National Research Council (IBBR-CNR), 80131 Napoli, Italy"},{"name":"Materias S.R.L., Corso N. Protopisani 70, 80146 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Anastasio","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, Unit of Food Hygiene, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-182X","authenticated-orcid":false,"given":"Pablo V.","family":"Escrib\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, 07122 Palma, Spain"},{"name":"Laminar Pharmaceuticals, 07121 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","first-page":"226","article-title":"On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. 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