Effect of Amphotericin B on the Metabolic Profiles of Candida albicans

被引:27
作者
Cao, YingYing [1 ]
Zhu, ZhenYu [1 ]
Chen, XiaoFei [1 ]
Yao, XiangWen [1 ]
Zhao, LiuYa [1 ]
Wang, Hui [1 ]
Yan, Lan [1 ]
Wu, HaiTang [1 ]
Chai, YiFeng [1 ]
Jiang, YuanYing [1 ]
机构
[1] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
Candida albicans; amphotericin B; metabolite; polyamine; OXIDATIVE STRESS-RESPONSE; SACCHAROMYCES-CEREVISIAE; ORNITHINE-DECARBOXYLASE; ANTIFUNGAL AGENTS; ANCHORED PROTEINS; RESISTANCE; TREHALOSE; EPIDEMIOLOGY; SPERMINE; TARGETS;
D O I
10.1021/pr4002178
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Amphotericin B (AmB) is a polyene antifungal drug widely used for systemic fungal infections. In this study, a metabonomic method using gas chromatography-mass spectrometry (GC/MS) was developed to characterize the metabolic profiles of Candida albicans cells exposed to AmB. Thirty-one differentially produced metabolites between AmB-treated and the control groups were identified, among which 10 metabolites were upregulated and 21 metabolites were downregulated. These differentially produced metabolites were mainly involved in polyamines synthesis, tricarboxylic acid (TCA) cycle, oxidative stress, glutathione metabolism, lipid synthesis and glycolysis. Further experiments showed that the polyamines including putrescine, spermidine, and spermine played an important role in the sensitivity of C. albicans cells upon AmB treatment, and combined use of AmB and inhibitors of polyamine biosynthesis pathway might be a potential antifungal strategy. This study provided a systemic view of the metabolic pattern in C. albicans upon exposure to AmB, which shed new light on the mechanisms of action of antifungal agents.
引用
收藏
页码:2921 / 2932
页数:12
相关论文
共 67 条
[1]   An update on antifungal targets and mechanisms of resistance in Candida albicans [J].
Akins, RA .
MEDICAL MYCOLOGY, 2005, 43 (04) :285-318
[2]   Protective role of trehalose during severe oxidative stress caused by hydrogen peroxide and the adaptive oxidative stress response in Candida albicans [J].
Alvarez-Peral, FJ ;
Zaragoza, O ;
Pedreño, Y ;
Argüelles, JC .
MICROBIOLOGY-SGM, 2002, 148 :2599-2606
[3]   Allicin enhances the oxidative damage effect of amphotericin B against Candida albicans [J].
An, MaoMao ;
Shen, Hui ;
Cao, YongBing ;
Zhang, JunDong ;
Cai, Yun ;
Wang, Rui ;
Jiang, YuanYing .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2009, 33 (03) :258-263
[4]  
[Anonymous], 1998, GUIDE POLYAMINES, P1
[5]   Physiological roles of trehalose in bacteria and yeasts:: a comparative analysis [J].
Argüelles, JC .
ARCHIVES OF MICROBIOLOGY, 2000, 174 (04) :217-224
[6]   Disruption of γ-glutamylcysteine synthetase results in absolute glutathione auxotrophy and apoptosis in Candida albicans [J].
Baek, YU ;
Kim, YR ;
Yim, HS ;
Kang, SO .
FEBS LETTERS, 2004, 556 (1-3) :47-52
[7]   Appropriate sampling for intracellular amino acid analysis in five phylogenetically different yeasts [J].
Bolten, Christoph J. ;
Wittmann, Christoph .
BIOTECHNOLOGY LETTERS, 2008, 30 (11) :1993-2000
[8]   AMPHOTERICIN-B - CURRENT UNDERSTANDING OF MECHANISMS OF ACTION [J].
BRAJTBURG, J ;
POWDERLY, WG ;
KOBAYASHI, GS ;
MEDOFF, G .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (02) :183-188
[9]   Quantitative Evaluation of Intracellular Metabolite Extraction Techniques for Yeast Metabolomics [J].
Canelas, Andre B. ;
ten Pierick, Angela ;
Ras, Cor ;
Seifar, Reza M. ;
van Dam, Jan C. ;
van Gulik, Walter M. ;
Heijnen, Joseph J. .
ANALYTICAL CHEMISTRY, 2009, 81 (17) :7379-7389
[10]   Polyamines protect Escherichia coli cells from the toxic effect of oxygen [J].
Chattopadhyay, MK ;
Tabor, CW ;
Tabor, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2261-2265