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options. In this context, antimicrobial peptides (AMPs) have been widely studied for their potent antimicrobial properties. In this study, we evaluated the anti-MRSA effect of a novel AMP, LyeTx I mn\u0394KL, derived from a toxin of Lycosa erythrognatha. Its activity was evaluated in vitro by minimal inhibitory and bactericidal concentrations (MIC and MBC), antibiofilm effect, membrane interaction, cytotoxicity, synergistic interaction with vancomycin, and in vivo in an MRSA murine wound\/abscess infection model. LyeTx I mn\u0394KL showed enhanced antimicrobial activity against clinical MRSA isolates compared to its prototype (LyeTx I mn\u0394K), with MIC50 and MBC50 of 2 and 8 \u00b5M and 16 and 32 \u00b5M, respectively. Furthermore, LyeTx I mn\u0394KL exhibited a rapid bactericidal effect and a pronounced ability to inhibit biofilm formation and disrupt mature biofilms. LyeTx I mn\u0394KL interacts with bacterial membranes, adopts an \u03b1-helical structure, and induces membrane disruption and leakage of intracellular material. In vivo, topical treatment with LyeTx I mn\u0394KL reduced MRSA burden compared with LyeTx I mn\u0394K and untreated controls (log10 CFU\/g of wound of 2.4, 4.4, and 6.5 for LyeTx I mn\u0394KL, LyeTx I mn\u0394K, and the saline group, respectively). However, increased cytotoxicity remains a significant limitation. Overall, LyeTx I mn\u0394KL is a promising anti-MRSA candidate for topical use with potent antibiofilm and in vivo activity.<\/jats:p>","DOI":"10.3390\/toxins18080323","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LyeTx I mn\u0394KL, a New Synthetic Peptide Derived from a Lycosa erythrognatha Toxin, with Potent In Vitro and In Vivo Activity Against Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-719X","authenticated-orcid":false,"given":"Waleska Stephanie","family":"da Cruz Nizer","sequence":"first","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu de Medicina e Biomedicina, Belo Horizonte 30260-070, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-8363","authenticated-orcid":false,"given":"Giulliana Altaf","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu de Medicina e Biomedicina, Belo Horizonte 30260-070, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8946-9363","authenticated-orcid":false,"given":"William Gustavo","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu de Medicina e Biomedicina, Belo Horizonte 30260-070, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-0342","authenticated-orcid":false,"given":"Felipe Henrique de Souza","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu de Medicina e Biomedicina, Belo Horizonte 30260-070, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanderson Aparecido Brand\u00e3o","family":"Candido","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-5966","authenticated-orcid":false,"given":"Amanda Neves","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3555-3275","authenticated-orcid":false,"given":"Giovanna Paula","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Moreira","family":"Verly","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-4032","authenticated-orcid":false,"given":"Maria Elena de","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa de Belo Horizonte, Programa de P\u00f3s-Gradua\u00e7\u00e3o Stricto Sensu de Medicina e Biomedicina, Belo Horizonte 30260-070, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104267","DOI":"10.1016\/j.resmic.2025.104267","article-title":"Staphylococcus aureus: Dynamics of Pathogenicity and Antimicrobial-Resistance in Hospital and Community Environments\u2014Comprehensive Overview","volume":"176","year":"2025","journal-title":"Res. 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