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DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain
Alternative TitleDNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain
Yan Lan1; Zhang Jundong1; Li Miaohai2; Cao Yongbing1; Xu Zheng1; Cao Yingying1; Gao Pinghui1; Wang Yan1; Jiang Yuanying1
2008
Source PublicationACTA BIOCHIMICA ET BIOPHYSICA SINICA
ISSN1672-9145
Volume40Issue:12Pages:1048-1060
AbstractSeveral 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.
Other AbstractSeveral 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.
KeywordDIFFERENTIAL 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
Indexed ByCSCD
Language英语
CSCD IDCSCD:3433831
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imr.ac.cn/handle/321006/158092
Collection中国科学院金属研究所
Affiliation1.安徽肥东花生原种场
2.中国科学院金属研究所
Recommended Citation
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.
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