临床白念珠菌耐药性与ERG3基因突变及表达的关系  

Correlation between the point mutations and high expression of ERG3 gene and drug resistance in clinical candida albicans

作　　者：陈晋宇[1] 冯文莉[1] 杨静[1] 奚志琴[1] 乔祖莎[1] 

机构地区：[1]山西医科大学第二临床医学院皮肤性病科,太原030001

出　　处：《国际医药卫生导报》2014年第13期1838-1844,共7页International Medicine and Health Guidance News

基　　金：山西省基础研究项目资助（2012011045-3）;山西省青年科技研究基金（2012021035-3）;山西医科大学科技创新基金（01201013）;山西省卫生厅科技攻关项目（201301009）

摘　　要：目的明确白念珠菌ERG3基因突变及高表达对抗真菌药物耐药的调控作用。方法用微量稀释法测得36株临床分离白念珠菌的最小抑菌浓度（MIC）；提取基因组DNA，PCR基因扩增，将扩增后的产物纯化测序，并与genbank中已知的标准序列（AF069572）进行BLAST比对分析；采用实时定量PCR（RT—PCR）方法，对白念珠菌ERG3基因表达的mRNA进行相对定量分析。结果36株白念珠菌ERG3基因序列共发现6个突变位点，其中19株发生同义突变，突变位点为T51C、T432C、T381C、C438T、T1044C；2株发生错义突变，突变位点为C1052T，并产生耐药；白念珠菌对氟康唑耐药组ERG3高表达的发生率高于敏感组（P〈0．05）。结论ERG3基因突变及高表达增加了抗真菌药物的耐药性。同时有多种调节机制共同参与白念珠菌耐药性的形成。Objective To investigate the correlation between the mutation and high expression of ERG3 to antifungal drug resistance in candida albicans. Methods Candida albicans was measured minimum inhibitory concentration （MIC） by microdilution susceptibility testing. DNA was extracted. PCR was carried out to amply the full-length ERG3. The purified ERG3 compared with known standard sequences in genbank （AF069572） through BLAST analysis. The mRNA expression of ERG3 was determined by reverse transcription-polymerase chain reaction （RT-PCR）. Results Six mutations were detected in ERG3 gene of thirty-Six candida albicans strains. Nineteen strains appeared synonymous-mutations, including T51C, T432C, T381C, C438T, T1044C. Two strains appeared missense mutation, including C 1052T. High expression rate of fluconazole resistant group was higher than that of the sensitive group. Conclusion The mutation and high expression of ERG3 genes increased antifungal drug resistance. Meanwhile, variety of regulating mechanism participate in the formation of drug resistance in candida albicans.

关 键 词：白念珠菌 ERG3基因 耐药性 

分 类 号：R440[医药卫生—诊断学]