Carrera-Aubesart, AdamLi, JiaruiContreras, EstefaníaBello Madruga, RobertoTorrent Burgas, MarcAndreu Martínez, David2024-11-152024-11-152024Carrera-Aubesart A, Li J, Contreras E, Bello-Madruga R, Torrent M, Andreu D. From in vitro promise to in vivo reality: An instructive account of infection model evaluation of antimicrobial peptides. Int J Mol Sci. 2024 Sep 10;25(18):9773. DOI: 10.3390/ijms251897731422-0067http://hdl.handle.net/10230/68698Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing 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.application/pdfeng© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/ijms25189773AMPsCrotalicidinInfectionMurine modelRetroenantioTopoisomersinfo:eu-repo/semantics/openAccess