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

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 lysi...

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Bibliographic Details
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:
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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
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-52721-0