DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain

IMR OpenIR

	DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain
其他题名	DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain
	Yan Lan 1; Zhang Jundong 1; Li Miaohai 2; Cao Yongbing 1; Xu Zheng 1; Cao Yingying 1; Gao Pinghui 1; Wang Yan 1; Jiang Yuanying 1
	2008
发表期刊	ACTA BIOCHIMICA ET BIOPHYSICA SINICA
ISSN	1672-9145
卷号	40 期号:12 页码:1048-1060
摘要	Several mechanisms are responsible for the acquired fluconazole (FLC) resistance in Candida albicans. In this study, we developed a FLC-resistant C. albicans strain through serial cultures of a FLC-susceptible C. albicans strain with inhibitory concentrations of FLC. Complimentary DNA microarray analysis and real-time reverse transcription-polymerase chain reaction were used to investigate gene expression changes during the acquisition of azole resistance in the susceptible parental strain and the resistant daughter strain. The differentially expressed genes represented functions as diverse as transporters (e.g. CDR1, PDR17), ergosterol biosynthesis (e.g. ERG2, ERG9), sterol metabolism (e.g. ARE2, IPF6464), energy metabolism (e.g. ADH3, AOX2) and transcription factors (e.g. FCR1, ECM22). Functional analysis revealed that energy-dependent efflux activity of membrane transporters increased and that ergosterol content decreased with the accumulation of sterol intermediates in the resistant strain as compared with the susceptible strain. We found that a point mutation (N977K) in transcription factor TAC1 that resulted in hyperactivity of Tac1 could be the reason for overexpression of CDR1, CDR2, and PDR17 in the resistant strain. Furthermore, a single amino acid difference (D19E) in ERG3 that led to the inactivation of Erg3 could account for both sterol precursor accumulation and the changes in the expression of ergosterol biosynthesis genes in this resistant strain. These findings expand the understanding of potential novel molecular targets of FLC resistance in clinical C. albicans isolates.
其他摘要	Several mechanisms are responsible for the acquired fluconazole (FLC) resistance in Candida albicans. In this study, we developed a FLC-resistant C. albicans strain through serial cultures of a FLC-susceptible C. albicans strain with inhibitory concentrations of FLC. Complimentary DNA microarray analysis and real-time reverse transcription-polymerase chain reaction were used to investigate gene expression changes during the acquisition of azole resistance in the susceptible parental strain and the resistant daughter strain. The differentially expressed genes represented functions as diverse as transporters (e.g. CDR1, PDR17), ergosterol biosynthesis (e.g. ERG2, ERG9), sterol metabolism (e.g. ARE2, IPF6464), energy metabolism (e.g. ADH3, AOX2) and transcription factors (e.g. FCR1, ECM22). Functional analysis revealed that energy-dependent efflux activity of membrane transporters increased and that ergosterol content decreased with the accumulation of sterol intermediates in the resistant strain as compared with the susceptible strain. We found that a point mutation (N977K) in transcription factor TAC1 that resulted in hyperactivity of Tac1 could be the reason for overexpression of CDR1, CDR2, and PDR17 in the resistant strain. Furthermore, a single amino acid difference (D19E) in ERG3 that led to the inactivation of Erg3 could account for both sterol precursor accumulation and the changes in the expression of ergosterol biosynthesis genes in this resistant strain. These findings expand the understanding of potential novel molecular targets of FLC resistance in clinical C. albicans isolates.
关键词	DIFFERENTIAL GENE-EXPRESSION GENOME-WIDE EXPRESSION SACCHAROMYCES-CEREVISIAE PROTEOMIC ANALYSIS ANTIFUNGAL AGENTS BIOSYNTHETIC-PATHWAY AZOLE RESISTANCE ANALYSIS REVEALS DRUG-RESISTANCE EFFLUX Candida albicans fluconazole resistance microarray
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:3433831
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/158092
专题	中国科学院金属研究所
作者单位	1.安徽肥东花生原种场 2.中国科学院金属研究所
推荐引用方式 GB/T 7714	Yan Lan,Zhang Jundong,Li Miaohai,et al. DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2008,40(12):1048-1060.
APA	Yan Lan.,Zhang Jundong.,Li Miaohai.,Cao Yongbing.,Xu Zheng.,...&Jiang Yuanying.(2008).DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,40(12),1048-1060.
MLA	Yan Lan,et al."DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 40.12(2008):1048-1060.