Cell selectivity-membrane phospholipids relationship of the antimicrobial effects shown by pleurocidin enantiomeric peptides.
Previously, we investigated the antimicrobial properties of pleurocidin (Ple) enantiomers. Our studies showed that the L-enantiomer exhibited about a 2-16 fold more potent activity against bacterial strains as compared to that of the D-enantiomer. However, fungal strains were about two-fold more susceptible to the D-enantiomer than to the L-enantiomer. In this study, confocal laser scanning microscopy indicates that the Ple enantiomers internalize into the cell surface. The present results also suggest that they could be characterized by a membrane-active mechanism. To further elucidate their selective membranolytic activities, we conducted a fluorescence analysis. A study with 1,6-diphenyl-1,3,5-hexatriene, a hydrophobic molecule, showed that the L-and the D-enantiomer exert more potent antibacterial or antifungal activity than their opposite enantiomer, respectively. Furthermore, we synthesized liposomes by using representative phospholipids consisting of bacterial or fungal membranes. Our results show that the L-enantiomer causes significant dye leakage from negatively charged liposomes (PG/CL; 58:42, PC/PG; 1:1, w/w) which mimic bacterial membranes such as Staphylococcus aureus. Conversely, the D-enantiomer has more potent leakage effects against fungal liposomes (PC/PE/PI/ergosterol; 5:4:1:2, w/w/w/w, PC/ergosterol; 10:1, w/w). In summary, these results suggest that the selective antimicrobial effects of the Ple enantiomers against bacterial and fungal cells may be due to the different lipid compositions of prokaryotes and eukaryotes.
Lee
Juneyoung
J
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
Park
Cana
C
Park
Seong-Cheol
SC
Woo
Eun-Rhan
ER
Park
Yoonkyung
Y
Hahm
Kyung-Soo
KS
Lee
Dong Gun
DG
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D029941:Fish Proteins / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013237:Stereoisomerism
D023181:Antimicrobial Cationic Peptides; D029941:Fish Proteins; D008081:Liposomes; C105851:pleurocidin