In Vivo Evaluation of ECP Peptide Analogues for the Treatment of Acinetobacter baumannii Infection

Jiarui Li, Guillem Prats-Ejarque, Marc Torrent, David Andreu, Klaus Brandenburg, Pablo Fernández-Millán, Ester Boix*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Article number386
Number of pages20
Issue number2
Publication statusPublished - 1 Feb 2022


  • AMPs
  • ECP
  • Gram-negative bacteria
  • Infection
  • LPS
  • Murine model
  • infection
  • murine model


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