Tandem Repeat of a Short Human Chemerin-Derived Peptide and Its Nontoxic D-Lysine-Containing Enantiomer Display Broad-Spectrum Antimicrobial and Antitubercular Activities

To design novel antimicrobial peptides by utilizing the sequence of the human host defense protein, chemerin, a seven-residue amphipathic stretch located in the amino acid region, 109-115, was identified, which possesses the highest density of hydrophobic and positively charged residues. Although this 7-mer peptide was inactive toward microorganisms, its 14-mer tandem repeat (Chem-KVL) was highly active against different bacteria including methicillin-resistant Staphylococcus aureus, a multidrug-resistant Staphylococcus aureus strain, and slow- and fast-growing mycobacterial species. The selective enantiomeric substitutions of its two L-lysine residues were attempted to confer cell selectivity and proteolytic stability to Chem-KVL. Chem-8dK with a D-lysine replacement in its middle (eighth position) showed the lowest hemolytic activity against human red blood cells among Chem-KVL analogues and maintained high antimicrobial properties. Chem-8dK showed in vivo efficacy against Pseudomonas aeruginosa infection in BALB/c mice and inhibited the development of resistance in this microorganism up to 30 serial passages and growth of intracellular mycobacteria in THP-1 cells.

Automated summary

By designing novel antimicrobial peptides based on the sequence of the human host defense protein chemerin, researchers identified a seven-residue amphipathic stretch with high density of hydrophobic and positively charged residues. A 14-residue tandem repeat derived from this stretch showed high activity against various bacteria and potential for use in combating infections.