Projects per year
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.
Original language | English |
---|---|
Article number | 386 |
Number of pages | 20 |
Journal | Biomedicines |
Volume | 10 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Feb 2022 |
Keywords
- AMINO-ACIDS
- AMPs
- ANTIMICROBIAL PEPTIDES
- COLISTIN
- ECP
- Gram-negative bacteria
- Infection
- LIPOPOLYSACCHARIDE
- LPS
- MODEL
- Murine model
- PROTEASE STABILITY
- infection
- murine model
Fingerprint
Dive into the research topics of 'In Vivo Evaluation of ECP Peptide Analogues for the Treatment of Acinetobacter baumannii Infection'. Together they form a unique fingerprint.-
NON CODING RNA CLEAVAGE IN HOST DEFENCE AGAINST INFECTION (NCRNA-INFECT)
Boix Borras, E., ANGUITA CONTRERAS, R., Bhakta, S., Li, J., Lu ., L., Prats Ejarque, G., ROSENBERG, H., SALAZAR MONTOYA, V., SPYROULIAS, G., Fernandez Millan, P. & Moussaoui Keribii, M.
1/06/20 → 31/05/23
Project
-
Pattern recognition of non-coding RNA's to search for novel therapeutic targets in the fight against bacterial antimicrobial resistance
Boix Borras, E., Barbosa Perez, S., Fernandez Millan, P., Moussaoui Keribii, M., Nogués Bara, M. V., Prats Ejarque, G., Pulido Gomez, P. & Vergara Esteras, P.
25/02/19 → 24/02/22
Project