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

发布时间：2019-05-20 10:53

【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(P0.05);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)(P0.05),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。
[Abstract]:Objective to investigate the effect of ERG11 gene mutation and high expression on cross-resistance of azole drugs in Pseudomonas albicans, so as to provide theoretical basis for rational use of drugs in clinic. Methods 43 clinical strains of candida albicans were collected from September 2014 to October 2015 for drug sensitivity test in vitro. ERG11 gene was amplified by polymerase chain reaction (PCR) and sequenced, and its mutation was analyzed. The expression of ERG11 gene mRNA was detected by real-time fluorescence quantitative PCR (RT-PCR). Results among the 43 experimental strains, there were 15 drug-sensitive strains, 13 single drug-resistant strains and 15 cross-resistant strains. Among them, 9 cross-resistant strains showed 5 missense mutations, which were T123I, Y132H, E174A, G450E and G464S, respectively. The mutation probability of ERG11 gene in cross-resistant strains was significantly higher than that in single drug-resistant strains and drug-sensitive strains (P 0.05). The expression of ERG11 gene mRNA in cross-resistant strain (4.00 卤2.06) was significantly higher than that in drug-sensitive strain (0.93 卤0.21) (P 0.05), but there was no significant difference between cross-resistant strain and single drug-resistant strain (3.92 卤1.01). Conclusion the mutation and high expression of ERG11 gene are the mechanism of drug resistance of candida albicans. The relationship between cross resistance and gene mutation remains to be further studied.
【作者单位】：山西医科大学第二医院皮肤性病科;
【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)
【分类号】：R446.5

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