白色假丝酵母菌ERG11基因突变与高表达在唑类药物交叉耐药中的作用  

Role of mutation and over-expression of ERG11 gene in Candida albicans in cross-resistance to azoles

作　　者：乔祖莎[1] 冯文莉[1] 杨静[1] 奚志琴[1] 马彦[1] 张谨宇[1] 

机构地区：[1]山西医科大学第二医院皮肤性病科,山西太原030001

出　　处：《中华医院感染学杂志》2016年第20期4594-4597,共4页Chinese Journal of Nosocomiology

基　　金：山西医科大学第二医院青年基金项目(20140101);山西医科大学校级青年基金项目(02201420);山西省卫生厅科技攻关项目(201301009)

摘　　要：目的初步探讨白色假丝酵母菌ERG11基因突变、高表达对唑类药物交叉耐药的作用,为临床合理用药提供理论依据。方法自2014年9月-2015年10月收集43株白色假丝酵母菌临床菌株进行体外药物敏感性试验,聚合酶链反应(PCR)扩增ERG11基因并测序、分析其突变情况,实时荧光定量PCR(RT-PCR)检测ERG11基因mRNA的表达水平。结果 43株实验菌株中有药物敏感菌株15株、单药耐药菌株13株、交叉耐药菌株15株,其中9株交叉耐药菌株出现5个错义突变,分别为T123I、Y132H、E174A、G450E、G464S,交叉耐药菌株ERG11基因突变概率显著高于单药耐药菌株及药物敏感菌株(P<0.05);交叉耐药菌株ERG11基因mRNA的表达量(4.00±2.06)显著高于药物敏感菌株(0.93±0.21)(P<0.05),但与单药耐药菌株(3.92±1.01)相比无统计学差异。结论 ERG11基因突变及高表达均为白色假丝酵母菌耐药的机制,其交叉耐药的产生与基因突变相关,与高表达关系尚待进一步研究。OBJECTIVE To preliminarily explore the role of the mutation and over-expression of ERGll gene in Candida albicans in cross-resistant to azoles so as to provide theoretical basis for reasonable clinical use of antibi- otics. METHODS The in vitro drug susceptibility testing was performed for 43 clinical C. albicans isolates that were collected from Sep 2014 to Oct 2015, then the ERGll gene was amplified by using polymerase-chain-reaction （PCR） and was sequenced, the mutation of the ERGll gene was analyzed, and the level of expression of mRNA of the ERGll gene was detected with the use of real-time fluorescence quantitative PCR （RT-PCR）. RESULTS Of the 43 experimental strains, 15 were drug-susceptible, 13 were single drug-resistant, and 15 were cross-resistant five missense mutations, including T123I, Y132H, E174A, G450E and G464S, were identified in 9 cross-resistant strains. The rate of the ERGll gene mutation in the cross-resistant strains was significantly higher than that in the drug-susceptible strains and single drug-resistant strains （P〈0.05）. The expression level of mRNA of ERGll gene was （4.00±2.06） in the cross-resistant strains, significantly higher than （0.93±0.21） in the drug-suscepti- ble strains, however, there was no significant difference between the cross-resistant strains and the single drug-re- sistant strains （3.92±1.01）. CONCLUSION Both the mutation and over-expression of the ERGll gene are the drug resistance mechanisms of the C. albicans, the cross-resistance is associated with the gene mutation, however, the correlation with the over-expression needs to be further studied.

关 键 词：白色假丝酵母菌 交叉耐药 ERG11基因 基因突变 基因高表达 

分 类 号：R379[医药卫生—病原生物学]