title: Candidacidal mechanism of the arenicin-3-derived peptide NZ17074 from Arenicola marina.
abstract: The candidacidal mechanisms of NZ17074, which is a variant of arenicin-3 from Arenicola marina, against human pathogenic fungus Candida albicans are reported in this work. The minimum inhibitory concentration (MIC) of NZ17074 toward C. albicans was 4 μg/ml, and this peptide exerted marked candidacidal activity in an energy-dependent and salt-sensitive manner. The flow cytometric analysis using propidium iodide (PI) showed that the plasma membrane of cells treated with NZ17074 was perturbed and that the cells were arrested in the G2/M phase. The dihydrorhodamine-123 (DHR-123) staining showed that the reactive oxygen species (ROS) production of C. albicans increased after exposure to NZ17074. Typical cellular disruption events, such as mitochondrial degradation, nuclear fragmentation, nuclear membrane disruption, and chromatin condensation, were further revealed through rhodamine 123 (RH123) staining, 4',6-diamidino-2-phenylindole (DAPI) staining, and transmission electron microscopy. In addition, the intracellular localization of this peptide was concentration dependent: it was located in the membrane at low concentrations (4 to 8 μg/ml) and penetrated into the cytoplasm at high concentrations (16 to 32 μg/ml). Our results suggested that NZ17074 exerts its candidacidal effects by disrupting the cell membrane, inducing apoptosis, and interrupting the cell cycle. These findings showed the potential of NZ17074 as a new candidacidal peptide, in addition to its antibacterial activities.
authors.affiliation: Key Laboratory of Feed Biotechnology, Ministry of Agriculture, Beijing, 100081, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wang
authors.forename: Da
authors.initials: D
authors.lastname: Teng
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Mao
authors.forename: Di
authors.initials: D
authors.lastname: Xi
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D011077:Polychaeta / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; C000592841:NZ17074; D017382:Reactive Oxygen Species