Mechanism of Action and Therapeutic Potential of the β-Hairpin Antimicrobial Peptide Capitellacin from the Marine Polychaeta Capitella teleta

• Published in: Marine drugs Vol. 20; no. 3; p. 167
• Main Authors: Safronova, Victoria N, Panteleev, Pavel V, Sukhanov, Stanislav V, Toropygin, Ilia Y, Bolosov, Ilia A, Ovchinnikova, Tatiana V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-02-2022; MDPI
• Subjects: Amino acids; Analogs; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; antibiofilm activity; Antibiotics; Antimicrobial agents; antimicrobial peptide; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - isolation & purification; Antimicrobial Peptides - pharmacology; antimicrobial resistance; Aquatic Organisms - chemistry; Bacteria; Biofilms; Biofilms - drug effects; Biological activity; Capitella; capitellacin; Cell Line; Cell Membrane Permeability - drug effects; Chromatography; Cytotoxicity; Detergents; Disulfide bonds; Drug development; Drug resistance; E coli; Electrochemistry; Erythrocytes - drug effects; Escherichia coli - drug effects; Escherichia coli - physiology; Fibroblasts - drug effects; Gram-negative bacteria; Hemolysis - drug effects; Humans; Hydrophobicity; Invertebrates; Lipid bilayers; Lipids; Mammalian cells; Mammals; Membranes; Mimicry; Molecular structure; Pathogens; Peptides; Polychaeta - chemistry; Protein Conformation; Proteins; site-directed mutagenesis; Toxicity; site-directed mutagenesis; capitellacin; antimicrobial peptide; antimicrobial resistance; antibiofilm activity
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20030167

Among the most potent and proteolytically resistant antimicrobial peptides (AMPs) of animal origin are molecules forming a β-hairpin structure stabilized by disulfide bonds. In this study, we investigated the mechanism of action and therapeutic potential of the β-hairpin AMP from the marine polychaeta
, named capitellacin. The peptide exhibits a low cytotoxicity toward mammalian cells and a pronounced activity against a wide range of bacterial pathogens including multi-resistant bacteria, but the mechanism of its antibacterial action is still obscure. In view of this, we obtained analogs of capitellacin and tachyplesin-inspired chimeric variants to identify amino acid residues important for biological activities. A low hydrophobicity of the β-turn region in capitellacin determines its modest membranotropic activity and slow membrane permeabilization. Electrochemical measurements in planar lipid bilayers mimicking the
membrane were consistent with the detergent-like mechanism of action rather than with binding to a specific molecular target in the cell. The peptide did not induce bacterial resistance after a 21-day selection experiment, which also pointed at a membranotropic mechanism of action. We also found that capitellacin can both prevent
biofilm formation and destroy preformed mature biofilms. The marked antibacterial and antibiofilm activity of capitellacin along with its moderate adverse effects on mammalian cells make this peptide a promising scaffold for the development of drugs for the treatment of chronic
infections, in particular those caused by the formation of biofilms.