In vivo evaluation of ECP peptide analogues for the treatment of Acinetobacter baumannii infection
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- dc.contributor.author Li, Jiarui
- dc.contributor.author Prats-Ejarque, Guillem
- dc.contributor.author Torrent Burgas, Marc
- dc.contributor.author Andreu Martínez, David
- dc.contributor.author Brandenburg, Klaus
- dc.contributor.author Fernández-Millán, Pablo
- dc.contributor.author Boix, Ester
- dc.date.accessioned 2022-03-07T07:34:42Z
- dc.date.available 2022-03-07T07:34:42Z
- dc.date.issued 2022
- dc.description.abstract Antimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was designed that combines antimicrobial action against Gram-negative species with lipopolysaccharides (LPS) binding and endotoxin-neutralization activities. Next, analogues that contain non-natural amino acids were designed to increase serum stability. Here, two analogues were selected for in vivo assays: the all-D version (ECPep-D) and the Arg to Orn version that incorporates a D-amino acid at position 2 (ECPep-2D-Orn). The peptide analogues retained high LPS-binding and anti-endotoxin activities. The peptides efficacy was tested in a murine acute infection model of Acinetobacter baumannii. Results highlighted a survival rate above 70% following a 3-day supervision with a single administration of ECPep-D. Moreover, in both ECPep-D and ECPep-2D-Orn peptide-treated groups, clinical symptoms improved significantly and the tissue infection was reduced to equivalent levels to mice treated with colistin, used as a last resort in the clinics. Moreover, treatment drastically reduced serum levels of TNF-α inflammation marker within the first 8 h. The present results support ECP-derived peptides as alternative candidates for the treatment of acute infections caused by Gram-negative bacteria.
- dc.description.sponsorship Research work was supported by Fundació La Marató de TV3 (TV3-201803-10), the Ministerio de Economía y Competitividad (PID2019-106123GB-I00) and by AGAUR, Generalitat de Catalunya (2016PROD00060; 2019 LLAV 00002), co-financed by FEDER funds. P.F.-M. was a recipient of Juan de la Cierva postdoctoral fellowship, G.P.-E. was recipient of a PIF-UAB predoctoral fellowship and J.L. was a recipient of a CSC predoctoral fellowship.
- dc.format.mimetype application/pdf
- dc.identifier.citation Li J, Prats-Ejarque G, Torrent M, Andreu D, Brandenburg K, Fernández-Millán P, Boix E. In vivo evaluation of ECP peptide analogues for the treatment of Acinetobacter baumannii infection. Biomedicines. 2022 Feb 5;10(2):386. DOI: 10.3390/biomedicines10020386
- dc.identifier.doi http://dx.doi.org/10.3390/biomedicines10020386
- dc.identifier.issn 2227-9059
- dc.identifier.uri http://hdl.handle.net/10230/52633
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Biomedicines. 2022 Feb 5;10(2):386
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106123GB-I00
- dc.rights © 2022 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 (http://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 ECP
- dc.subject.keyword Gram-negative bacteria
- dc.subject.keyword LPS
- dc.subject.keyword Infection
- dc.subject.keyword Murine model
- dc.title In vivo evaluation of ECP peptide analogues for the treatment of Acinetobacter baumannii infection
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion