Li, JiaruiPrats-Ejarque, GuillemTorrent Burgas, MarcAndreu Martínez, DavidBrandenburg, KlausFernández-Millán, PabloBoix, Ester2022-03-072022-03-072022Li 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/biomedicines100203862227-9059http://hdl.handle.net/10230/52633Antimicrobial 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.application/pdfeng© 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/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/biomedicines10020386AMPsECPGram-negative bacteriaLPSInfectionMurine modelinfo:eu-repo/semantics/openAccess