Enhancement effect of N-methyl-N″-dodecylguanidine on the vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans
Enhancement effect of N-methyl-N″-dodecylguanidine on the vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans
复制标题
N-甲基-N"-十二烷基胍对两性霉素B真空靶向杀菌对病原真菌白色念珠菌活性的增强作用
DOI：
10.1038/ja.2011.31
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Toshio Tanaka
中科院分区：
文献类型：
--
作者：
Masahiro Yutani;A. Ogita;Y. Usuki;Ken;Toshio Tanaka
奈菲霉素（niphimycin， NM）多醇内酯环上的烷基胍链被认为是奈菲霉素具有液泡膜断裂和氧化应激诱导的杀真菌活性的必要条件。在培养基中添加n -甲基- n″-十二烷基胍可以增强两性霉素B （AmB）对酿酒酵母细胞的液泡靶向杀菌活性，其中内酯环没有烷基胍链。本研究考察了n -甲基- n″-十二烷基胍在37℃RPMI 1640培养基中增强AmB对白色念珠菌液泡靶向杀菌活性的作用。n -甲基- n″-十二烷基胍对白色念珠菌细胞具有致死性，并增强了AmB对这种致病真菌的液泡破坏活性。n -甲基- n″-十二烷基胍以剂量依赖的方式增加细胞活性氧的产生，但其对AmB致死的增强作用并不伴随着氧化应激诱导的扩增。无论是单独用致死浓度的H2O2处理，还是用亚致死浓度的H2O2与AmB联合处理，真菌液泡都受到保护，免受破坏性损伤。当细胞用麦角甾醇预处理时，n -甲基- n″-十二烷基胍对增强AmB致死性或AmB诱导的液泡破坏无效。因此，麦角甾醇依赖机制被认为是n -甲基- n″-十二烷基胍增强白色念珠菌细胞中AmB液泡靶向杀真菌活性的可能靶点。
The alkylguanidium chain attached to the polyol lactone ring of niphimycin (NM) is considered a requisite for the fungicidal activity of NM characterized by vacuole membrane fragmentation and oxidative stress induction. The addition of N-methyl-N″-dodecylguanidine to the medium can enhance the vacuole-targeting fungicidal activity of amphotericin B (AmB), in which the lactone ring has no such alkylguanidium chain, on Saccharomyces cerevisiae cells. In this study, the enhancement effect of N-methyl-N″-dodecylguanidine on the vacuole-targeting fungicidal activity of AmB was examined against Candida albicans in RPMI 1640 medium at 37 °C. N-methyl-N″-dodecylguanidine was lethal to C. albicans cells and additionally enhanced the vacuole disruptive activity of AmB against this pathogenic fungus. N-methyl-N″-dodecylguanidine elevated the generation of cellular reactive oxygen species when added alone in a dose-dependent manner, but its enhancement effect on AmB lethality did not accompany amplification of oxidative stress induction. The fungal vacuoles were protected against the disruptive damage even if cells were treated with H2O2 alone at a lethal concentration or treated with H2O2 at a sublethal concentration in combination with AmB. N-methyl-N″-dodecylguanidine was ineffective in enhancing AmB lethality or AmB-induced vacuole disruption when cells had been pretreated with ergosterol. Ergosterol-dependent mechanism is thus considered to be a possible target of N-methyl-N″-dodecylguanidine in enhancing the vacuole-targeting fungicidal activity of AmB in C. albicans cells.
影响因子：
5.5
作者：
Okamoto, Y;Aoki, S;Mataga, I
通讯作者：
Mataga, I