Scientists tweaked the human antimicrobial peptide LL-37 to make versions that target specific bacteria while being less harmful to human cells. By changing the balance of charged and water‑repelling parts of the molecule, they created a new peptide called merecidin that can kill drug‑resistant Staph infections in an insect model without hurting the host.

There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17-32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and negative bacteria. By reducing the hydrophobic content, we previously succeeded in converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, our results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (<i>Galleria mellonella</i>) from the infection of methicillin-resistant <i>S. aureus</i> USA300. These new selective peptides constitute interesting candidates for future development.