Modified CLEC3A-Derived Antimicrobial Peptides Lead to Enhanced Antimicrobial Activity against Drug-Resistant Bacteria

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs...

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Bibliographic Details
Published in:Antibiotics (Basel) 2023-10, Vol.12 (10), p.1532
Main Authors: Meinberger, Denise, Drexelius, Marco G, Grabeck, Joshua, Hermes, Gabriele, Roth, Annika, Elezagic, Dzemal, Neundorf, Ines, Streichert, Thomas, Klatt, Andreas R
Format: Article
Language:English
Subjects:
Amino acids
Antibiotics
Antimicrobial activity
Antimicrobial agents
Antimicrobial peptides
Bacteria
Bacterial infections
Biocompatibility
C-type lectin
Cartilage
CLEC3A
Cytotoxicity
Drug resistance
drug-resistant bacteria
Glycine
Gram-negative bacteria
Gram-positive bacteria
Health aspects
Methicillin
MRSA
peptide modification
Peptides
Tryptophan
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Summary:Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their sequences, inserting a triple-glycine linker, adding an N-terminal tryptophan residue, and generating a D-amino acid variant, resulting in the generation of seven new peptides. We investigated their antimicrobial activity against gram-positive and gram-negative bacteria, their cytotoxicity to murine cells, and the biostability of the modified peptides in serum. We identified a novel antimicrobial peptide, WRK-30, with enhanced antimicrobial potency against S. aureus and MRSA. Additionally, WRK-30 was less cytotoxic to eukaryotic cells, allowing its application in higher concentrations in an in vivo setting. In conclusion, we identified a novel CLEC3A-derived antimicrobial peptide WRK-30 with significantly improved therapeutic properties and the potential to widen the repertoire of conventional antibiotics.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics12101532