Design of a novel analogue peptide with potent antibiofilm activities against Staphylococcus aureus based upon a sapecin B-derived peptide

• Published in: Scientific reports 2024-01, Vol.14 (1), p.2256-14, Article 2256
• Main Authors: Akhash, Nasim, Farajzadeh Sheikh, Ahmad, Farshadzadeh, Zahra
• Format: Article
• Language: English
• Subjects: 631/154; 631/326; Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibiotic resistance; Antimicrobial peptides; Biofilms; Drug resistance; Humanities and Social Sciences; Humans; Hydrophobicity; Lysine; Medical instruments; Methicillin; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Minimum inhibitory concentration; multidisciplinary; Peptides; Peptides - pharmacology; Proteolysis; Science; Science (multidisciplinary); Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus infections; Tryptophan
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-52721-0

Nowadays, antimicrobial peptides are promising to confront the existing global crisis of antibiotic resistance. Here, a novel analogue peptide (mKLK) was designed based upon a D-form amidated sapecin B-derived peptide (KLK) by replacing two lysine residues with two tryptophan and one leucine by lysine, and inserting one alanine. The mKLK displayed superior amphipathic helixes in which the most of hydrophobic residues are confined to one face of the helix and had a higher hydrophobic moment compared with KLK. The mKLK retained its antibacterial activity and structure in human serum, suggesting its stability to proteolytic degradation. The values of MIC and MBC for mKLK were equal to those of KLK against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). However, mKLK showed more capability of in vitro inhibiting, eradicating, and dispersing MRSA and MSSA biofilms compared with KLK. Furthermore, a remarkable inhibitory activity of mKLK against MRSA and MSSA biofilms was seen in the murine model of catheter-associated biofilm infection. Results of this study show that mKLK not only exhibits antibacterial activity and serum stability but also a potent biofilm inhibitory activity at sub-MIC concentrations, confirming its potential therapeutic advantage for preventing biofilm-associated MRSA and MSSA infections.