摘要: Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, and
Candida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment of
fungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increased
incidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drug
resistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale gene
expression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates from
bone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentially
expressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly,
the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genes
involved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups of
genes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stress
response genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes
(CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates.
Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5,
such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. These
findings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.
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分类:
生物学
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生物医药
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引用:
ChinaXiv:201703.01016
(或此版本
ChinaXiv:201703.01016V1)
doi:10.12074/201703.01016
CSTR:32003.36.ChinaXiv.201703.01016.V1
- 推荐引用方式:
Xu, Zheng,Zhang, Li-Xin,Zhang, Jun-Dong,Cao, Yong-Bing,Yu, an-Yuan Yu,Wang, De-Jun,Ying, Kang,Chen, Wan-Sheng,Jiang, Yuan-Ying.(2017).cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients.中国科学院科技论文预发布平台.[ChinaXiv:201703.01016]
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