Modified CLEC3A-Derived Antimicrobial Peptides Lead to Enhanced Antimicrobial Activity against Drug-Resistant Bacteria
Denise Meinberger,
Marco G. Drexelius,
Joshua Grabeck,
Gabriele Hermes,
Annika Roth,
Dzemal Elezagic,
Ines Neundorf,
Thomas Streichert,
Andreas R. Klatt
Affiliations
Denise Meinberger
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Marco G. Drexelius
Institute for Biochemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Joshua Grabeck
Institute for Biochemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Gabriele Hermes
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Annika Roth
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Dzemal Elezagic
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Ines Neundorf
Institute for Biochemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Cologne, Zuelpicher Str. 47a, 50674 Cologne, Germany
Thomas Streichert
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Andreas R. Klatt
Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany
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.
