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
[31]   INHIBITION OF THE DIMORPHIC TRANSITION OF CANDIDA-ALBICANS BY THE ORNITHINE DECARBOXYLASE INHIBITOR 1,4-DIAMINOBUTANONE - ALTERATIONS IN THE GLYCOPROTEIN COMPOSITION OF THE CELL-WALL [J].
MARTINEZ, JP ;
LOPEZRIBOT, JL ;
GIL, ML ;
SENTANDREU, R ;
RUIZHERRERA, J .
JOURNAL OF GENERAL MICROBIOLOGY, 1990, 136 :1937-1943
[32]   Reduced nephrotoxicity of conventional amphotericin B therapy after minimal nephroprotective measures:: Animal experiments and clinical study [J].
Mayer, J ;
Doubek, M ;
Doubek, J ;
Horky, D ;
Scheer, P ;
Stepánek, M .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (03) :379-388
[33]   Spermidine regulates Vibrio cholerae biofilm formation via transport and signaling pathways [J].
McGinnis, Marcus W. ;
Parker, Zachary M. ;
Walter, Nicholas E. ;
Rutkovsky, Alex C. ;
Cartaya-Marin, Claudia ;
Karatan, Ece .
FEMS MICROBIOLOGY LETTERS, 2009, 299 (02) :166-174
[34]  
McNemar MD, 1997, YEAST, V13, P1383
[35]   The GPI-modified proteins Pga59 and Pga62 of Candida albicans are required for cell wall integrity [J].
Moreno-Ruiz, Emilia ;
Ortu, Giuseppe ;
de Groot, Piet W. J. ;
Cottier, Fabien ;
Loussert, Celine ;
Prevost, Marie-Christine ;
de Koster, Chris ;
Klis, Frans M. ;
Goyard, Sophie ;
d'Enfert, Christophe .
MICROBIOLOGY-SGM, 2009, 155 :2004-2020
[36]   Mechanism of fluconazole resistance in Candida albicans biofilms:: Phase-specific role of efflux pumps and membrane sterols [J].
Mukherjee, PK ;
Chandra, J ;
Kuhn, DA ;
Ghannoum, MA .
INFECTION AND IMMUNITY, 2003, 71 (08) :4333-4340
[37]   Yeast sphingolipid bypass mutants as indicators of antifungal agents selectively targeting sphingolipid synthesis [J].
Nagiec, MM ;
Young, CL ;
Zaworski, PG ;
Kobayashi, SD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 307 (02) :369-374
[38]   'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data [J].
Nicholson, JK ;
Lindon, JC ;
Holmes, E .
XENOBIOTICA, 1999, 29 (11) :1181-1189
[39]   Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans [J].
Noble, SM ;
Johnson, AD .
EUKARYOTIC CELL, 2005, 4 (02) :298-309
[40]   Enhancement of amphotericin B activity against Candida albicans by superoxide radical [J].
Okamoto, Y ;
Aoki, S ;
Mataga, I .
MYCOPATHOLOGIA, 2004, 158 (01) :9-15