Fungicidal effect of pleurocidin by membrane-active mechanism and design of enantiomeric analogue for proteolytic resistance.
Pleurocidin (Ple) is a 25-residue peptide which is derived from the skin mucous secretion of the winter flounder (Pleuronectes americanus). In this study, we investigated antifungal effects and its mode of action of Ple on human pathogenic fungi. Ple showed potent antifungal activity with low hemolytic activity. To investigate the antifungal mechanisms of Ple, the cellular localization and membrane interaction of Ple were examined. Protoplast regeneration and membrane-disrupting activity by DPH-labeled membrane support the idea, that Ple exerts fungicidal activity against the human pathogenic fungus Candida albicans with the disruption of a plasma membrane. To aim for which was the application of a therapeutic agent, we designed a synthetic enantiomeric peptide composed of all-d-amino acids to enhance proteolytic resistance. The synthetic all-d-Ple also displayed two-fold more potent antifungal activity than that of all-l-Ple, and its antifungal activity showed proteolytic resistance against various proteases. Therefore, these results suggest a therapeutic potential of all-d-Ple with regard to its proteolytic resistance against human fungal infections.
Jung
Hyun Jun
HJ
Department of Microbiology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Puk-ku, Daegu 702-701, Republic of Korea.
Park
Yoonkyung
Y
Sung
Woo Sang
WS
Suh
Bo Kyoung
BK
Lee
Juneyoung
J
Hahm
Kyung-Soo
KS
Lee
Dong Gun
DG
D000935:Antifungal Agents / Q000633:toxicity*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002473:Cell Wall / Q000502:physiology; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D011523:Protoplasts / Q000502:physiology
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D029941:Fish Proteins; C105851:pleurocidin