Design and characterization of chionodracine-derived antimicrobial peptides with enhanced activity against drug-resistant human pathogens.

Starting from the sequence of the amphipathic α-helix of chionodracine (Cnd, 22 amino acids), we designed a series of mutants to increase Cnd's antimicrobial activity and selectivity toward prokaryotic cells and drug-resistant bacterial pathogens. We characterized these new Cnd-derived peptides using fluorescence, CD spectroscopy, and transmission electron microscopy, studying their interactions with synthetic lipid vesicles and assaying their biological function against E. faecium , S. aureus , K. pneumoniae , A. baumannii , P. aeruginosa , and Enterobacter sp. Upon interaction with model membranes, these new peptides with higher net charges and hydrophobic moments adopt a helical conformation similar to Cnd. Notably, they display a low cytotoxic activity against human primary cells, a low hemolytic activity, but a significantly high bactericidal activity against drug-resistant bacterial pathogens. The low values of micromolar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) make these Cnd-derived peptides potential templates to develop antimicrobial agents against drug-resistant human pathogens.