In vitro and in vivo antimicrobial activity of a synthetic peptide derived from the C-terminal region of human chemokine CCL13 against Pseudomonas aeruginosa

• Published in: Peptides (New York, N.Y. : 1980) Vol. 94; pp. 49 - 55
• Main Authors: Cossio-Ayala, Mayte, Domínguez-López, Mariana, Mendez-Enriquez, Erika, Portillo-Téllez, María del Carmen, García-Hernández, Enrique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2017
• Subjects: Alternative antibiotic; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial Cationic Peptides - therapeutic use; Antimicrobial peptide; Circular dichroism; Cytotoxicity and hemolysis; Disease Models, Animal; Humans; Mice; Monocyte Chemoattractant Proteins - chemistry; Monocyte Chemoattractant Proteins - metabolism; Monocyte Chemoattractant Proteins - pharmacology; Oligopeptides - pharmacology; Oligopeptides - therapeutic use; Peptide Fragments; Pneumonia; Pneumonia, Bacterial - drug therapy; Protein Domains; Pseudomonas aeruginosa - drug effects; Pseudomonas Infections - drug therapy; Cytotoxicity and hemolysis; TFE; Pneumonia; CFU; AMP; GSS and GCCL1357-75; CCL1357-75/CDAP-4; GPa and GCCL1357−75Pa; Alternative antibiotic; LPS; Antimicrobial peptide; Circular dichroism
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2017.06.006

•The antimicrobial activity of a peptide derived from human chemokine CCL13 was assessed.•CCL1357-75 disrupted the P. aeruginosa membrane, adopting a helical conformation.•No hemolytic or cytotoxic effect of CCL1357-75 on human cells was detected in vitro.•CCL1357-75 enhanced survival and diminished lung damage in a murine model of pneumonia.•CCL1357-75 ameliorated neutrophil recruitment and the production of inflammatory factors. Chemokines are important mediators of immunological responses during inflammation and under steady-state conditions. In addition to regulating cell migration, some chemotactic cytokines have direct effects on bacteria. Here, we characterized the antibacterial ability of the synthetic oligopeptide CCL1357-75, which corresponds to the carboxyl-terminal region of the human chemokine CCL13. In vitro measurements indicated that CCL1357-75 disrupts the cell membrane of Pseudomonas aeruginosa through a mechanism coupled to an unordered-helicoidal conformational transition. In a murine pneumonic model, CCL1357-75 improved mouse survival and bacterial clearance and decreased neutrophil recruitment, proinflammatory cytokines and lung pathology compared with that observed in untreated infected animals. Overall, our study supports the ability of chemokines and/or chemokine-derived oligopeptides to act as direct defense agents against pathogenic bacteria and suggests their potential use as alternative antibiotics.