| DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain | |
| Alternative Title | DNA 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 Publication | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| ISSN | 1672-9145 |
| Volume | 40Issue:12Pages:1048-1060 |
| Abstract | 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. |
| Other Abstract | 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. |
| Keyword | 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 |
| Indexed By | CSCD |
| Language | 英语 |
| CSCD ID | CSCD:3433831 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.imr.ac.cn/handle/321006/158092 |
| Collection | 中国科学院金属研究所 |
| Affiliation | 1.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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