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resistance. However, many AMPs fail to progress into clinics due to unexpected difficulties found in preclinical in vivo phases. Our research has focused on crotalicidin (Ctn), an AMP from snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work, we evaluate the in vivo efficacy of both the native-sequence AMPs and their retroenantio counterparts in a murine infection model with Acinetobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogs either exhibit toxicity or lack efficacy when administered to mice. Our findings underscore the critical importance of in vivo infection model evaluation to fully calibrate the therapeutic potential of AMPs.<\/jats:p>","DOI":"10.3390\/ijms25189773","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T04:35:24Z","timestamp":1725942924000},"page":"9773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-1647","authenticated-orcid":false,"given":"Adam","family":"Carrera-Aubesart","sequence":"first","affiliation":[{"name":"Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-2790","authenticated-orcid":false,"given":"Estefan\u00eda","family":"Contreras","sequence":"additional","affiliation":[{"name":"Integrated Service for Laboratory Animals (SIAL), Faculty of Veterinary, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8474-3951","authenticated-orcid":false,"given":"Roberto","family":"Bello-Madruga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6567-3474","authenticated-orcid":false,"given":"Marc","family":"Torrent","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-6666","authenticated-orcid":false,"given":"David","family":"Andreu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41579-023-00877-3","article-title":"Bacterial Defences: Mechanisms, Evolution and Antimicrobial Resistance","volume":"21","author":"Smith","year":"2023","journal-title":"Nat. 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