Thrombocidin-1-derived antimicrobial peptide TC19 combats superficial multi-drug resistant bacterial wound infections.

Abstract

Antimicrobial peptides are considered promising candidates for the development of novel antimicrobial agents to combat infections by multi-drug-resistant (MDR) bacteria. Here, we describe the identification and characterization of the synthetic peptide TC19, derived from the human thrombocidin-1-derived peptide L3. Biophysical experiments into the interaction between TC19 and mimics of human and bacterial plasma membranes demonstrated that the peptide is highly selective for bacterial membranes. In agreement, TC19 combined low cytotoxicity towards human fibroblasts with efficient and rapid killing in human plasma of MDR strains of several bacterial species of the ESKAPE panel. In addition, TC19 induced minor resistance in vitro, neutralized pro-inflammatory activity of bacterial cell envelope components while displaying slight chemotactic activity for human neutrophils. Importantly, topical application of TC19-containing hypromellose gel significantly reduced numbers of viable methicillin-resistant Staphylococcus aureus (MRSA) and MDR Acinetobacter baumannii in a superficial wound infection in mice. Together, TC19 is an attractive candidate for further development as a novel agent against (MDR) bacterial skin wound infections.

• Authors: Martijn Riool, Anna de Breij, Paulus H S Kwakman, Elisabeth Schonkeren-Ravensbergen, Leonie de Boer, Robert A Cordfunke, Nermina Malanovic, Jan W Drijfhout, Peter H Nibbering, Sebastian A J Zaat
• Journal: Biochimica et biophysica acta. Biomembranes (Biochim Biophys Acta Biomembr) Vol. 1862 Issue 8 Pg. 183282 (08 01 2020) ISSN: 1879-2642 [Electronic] Netherlands
• PMID: 32376222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides

Topics

• Animals
• Anti-Bacterial Agents (chemistry, pharmacology)
• Antimicrobial Cationic Peptides (chemistry, pharmacology)
• Biofilms (drug effects)
• Cell Membrane (drug effects)
• Drug Resistance, Multiple, Bacterial (drug effects)
• Humans
• Methicillin-Resistant Staphylococcus aureus (drug effects, pathogenicity)
• Mice
• Skin (drug effects, microbiology, pathology)
• Wound Infection (drug therapy, genetics, microbiology, pathology)