The vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans and its enhancement by allicin

被引:31
作者
Borjihan, Hasibagan [1 ]
Ogita, Akira [1 ,2 ]
Fujita, Ken-ichi [1 ]
Hirasawa, Eiji [1 ]
Tanaka, Toshio [1 ]
机构
[1] Osaka City Univ, Dept Biol & Geosci, Grad Sch Sci, Sumiyoshi Ku, Osaka 5588585, Japan
[2] Osaka City Univ, Res Ctr Urban Hlth & Sports, Sumiyoshi Ku, Osaka 5588585, Japan
基金
日本学术振兴会;
关键词
amphotericin B; allicin; Candida albicans; vacuole; ALLYL-SULFUR-COMPOUND; SACCHAROMYCES-CEREVISIAE; POLYMYXIN-B; TRANSPORT; BIOSYNTHESIS; INHIBITION; DEPENDENCE; CU2+; ION;
D O I
10.1038/ja.2009.103
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In this study, the vacuole disruptive activity was evaluated as a cause of amphotericin B (AmB) lethality against the pathogenic fungus Candida albicans in terms of its enhancement by allicin, an allyl-sulfur compound from garlic. Vacuole disruption was observed in parallel to AmB-induced cell death when the antibiotic was used at a lethal concentration and at a non-lethal concentration in combination with allicin. Allicin did not enhance AmB-induced cell death and the accompanying vacuole disruption when the cells were incubated with exogenous ergosterol for its enrichment in the vacuole. The vacuoles isolated from intact cells could be directly disrupted by the action of AmB to the same extent in the absence and presence of allicin, whereas the organelles isolated from ergosterol-enriched cells were resistant to its direct disruptive action. AmB was similarly incorporated into the fungal cytoplasm in cells with or without ergosterol enrichment, supporting the fact that AmB-induced vacuole disruption depends on its direct disruptive action on the organelle. In agreement with these findings, allicin was found to inhibit ergosterol transport from the plasma membrane to the cytoplasm, which is considered to be a cellular protective response to AmB-induced vacuole disruption in S. cerevisiae. Our study suggests that AmB lethality against C. albicans depends at least in part on its vacuole disruptive activity under the physiological condition permissive for invasive growth of the fungus. The Journal of Antibiotics (2009) 62, 691-697; doi:10.1038/ja.2009.103; published online 30 October 2009
引用
收藏
页码:691 / 697
页数:7
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