TY - JOUR
T1 - Design and characterization of chionodracine-derived antimicrobial peptides with enhanced activity against drug-resistant human pathogens
AU - Olivieri, Cristina
AU - Bugli, Francesca
AU - Menchinelli, Giulia
AU - Veglia, Gianluigi
AU - Buonocore, Francesco
AU - Scapigliati, Giuseppe
AU - Stocchi, Valentina
AU - Ceccacci, Francesca
AU - Papi, Massimiliano
AU - Sanguinetti, Maurizio
AU - Porcelli, Fernando
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1039/C8RA08065H
DO - 10.1039/C8RA08065H
M3 - Article
AN - SCOPUS:85058537286
SN - 2046-2069
VL - 8
SP - 41331
EP - 41346
JO - RSC Advances
JF - RSC Advances
IS - 72
ER -