应用全基因组表达谱芯片研究特比奈芬诱导白念珠菌耐药前后基因的差异性表达

The differential gene expression between terbinafine-susceptible and experimentally induced terbinafine-resistant isolates of Candida albicans using genome-wide expression profile analysis

目的应用白念珠菌全基因组表达谱芯片比较特比萘芬体外诱导白念珠菌产生耐药性前后基因表达谱的差异,以了解白念珠菌对特比萘芬产生耐药性的相关基因。方法白念珠菌ATCC90028菌株在浓度倍增的特比萘芬诱导下形成耐药的白念珠菌ATCC90028-R株,应用白念珠菌全基因组表达谱芯片比较白念珠菌ATCC90028和ATCC90028-R株全基因组表达谱的差异。结果基因芯片共筛选出109个差异表达基因,与白念珠菌ATCC90028株比较,在ATCC90028-R株中有46个基因表达上调,有63个基因表达下调。结论白念珠菌对特比萘芬耐药性的产生可能与其分子转运和解毒相关基因表达的上调,以及有关蛋白质合成、能量生成、糖转运蛋白、细胞应激反应、金属离子平衡基因表达的下调密切相关。

Objective The changes in the gene expression profile of Candida albicans associated with the acquisition of experimentally induced resistance to terbinafine was studied by genomic expression profiling.MethodsC.albicans ATCC 90028 was passed in increasing concentrations of terbinafine to generate isolate ATCC 90028-R.Susceptibility testing revealed that ATCC 90028-R was highly resistant to terbinafine.The gene expression profile of ATCC 90028-R was compared with that of ATCC 90028 using DNA microarray analysis.ResultsUpon examination of MICs of antifungal compounds,it was found that ATCC 90028-R was resistant to terbinafine.By DNA microarray analysis,a total of 109 genes were found to be differentially expressed,46 genes were up-regulated in ATCC 90028-R,while 63 genes down-regulated by at least 100%.ConclusionsThe results suggest that the genes associated with the induced molecule transporter and detoxification,repressed protein synthesis,energy generation,sugar transporter,cell stress,and ionic homeostasis may contribute to terbinafine resistance.