From in vitro promise to in vivo reality: An instructive account of infection model evaluation of antimicrobial peptides
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- dc.contributor.author Carrera-Aubesart, Adam
- dc.contributor.author Li, Jiarui
- dc.contributor.author Contreras, Estefanía
- dc.contributor.author Bello Madruga, Roberto
- dc.contributor.author Torrent Burgas, Marc
- dc.contributor.author Andreu Martínez, David
- dc.date.accessioned 2024-11-15T07:14:56Z
- dc.date.available 2024-11-15T07:14:56Z
- dc.date.issued 2024
- dc.description.abstract Antimicrobial 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.
- dc.description.sponsorship Grants from MCIN, Spanish Ministry of Science and Innovation (PID2020-113184RB-C22/AEI/10.13039/501100011033 to D.A. and PID2020-114627RB-I00/AEI/10.13039/501100011033 to M.T. were funded by MCIN/AEI; PDC2021-121544-I00/AEI/10.13039/501100011033 to M.T. was funded by MCIN/AEI and European Union Next GenerationEU/PRTR). Work at UPF was also funded by La Caixa Health Foundation (project HR17_00409 to D.A.) and by the MCIN “María de Maeztu” Program for Units of Excellence in R&D (CEX2018-000792-M) to the UPF Department of Medicine and Life Sciences at (MELIS-UPF).
- dc.format.mimetype application/pdf
- dc.identifier.citation Carrera-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/ijms25189773
- dc.identifier.doi http://dx.doi.org/10.3390/ijms25189773
- dc.identifier.issn 1422-0067
- dc.identifier.uri http://hdl.handle.net/10230/68698
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Int J Mol Sci. 2024 Sep 10;25(18):9773
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-113184RB-C22
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114627RB-I00
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PDC2021-121544-I00
- dc.rights © 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword AMPs
- dc.subject.keyword Crotalicidin
- dc.subject.keyword Infection
- dc.subject.keyword Murine model
- dc.subject.keyword Retroenantio
- dc.subject.keyword Topoisomers
- dc.title From in vitro promise to in vivo reality: An instructive account of infection model evaluation of antimicrobial peptides
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion