白色念珠菌upc2基因G1927A多态性与唑类药物耐药的关系  

The relationship between azole drug resistance and G1927A polymorphism of upc2 gene in Candida albicans

作　　者：张晓云[1] 姜利群[1] 马巧玲[1] 

机构地区：[1]中国人民解放军第184医院检验科,江西鹰潭335000

出　　处：《现代预防医学》2016年第16期3016-3019,共4页Modern Preventive Medicine

基　　金：南京军区医学科技创新项目(No.12MA050)

摘　　要：目的探讨白色念珠菌upc2基因C末端单核苷酸多态性以及其对唑类药物耐药的影响。方法对34株白色念珠菌临床株,纸片法测定5种药物敏感性,DNA测序法检测upc2基因单核苷酸多态性,RT-PCR法测定cdr1基因m RNA转录水平。比较耐药株和敏感株upc2单核苷酸多态性以及cdr1基因m RNA水平的差异。结果 14株白色念珠菌氟康唑耐药株(3株多重耐药,6株双重耐药,5株单一耐药),20株敏感株对5种药物均敏感。5株耐药白色念珠菌upc2基因存在G1927A型多态性,20株敏感株upc2基因均为G1927野生型,G1927A型upc2基因检出率35.7%,显著高于敏感株(χ2=8.37,P<0.01)。G1927A型多重耐药株的cdr1基因m RNA水平高于G1927A型双重耐药株,并且二者均高于敏感株。结论 upc2基因G1927A单核苷酸多态性通过上调cdr1基因m RNA转录而引起白色念珠菌对唑类药物产生多重耐药或双重耐药表型。Objective This work was to investigate the polymorphism of upc2 gene c-terminal domain and the effect of the polymorphism on azole drug resistance in Candida albicans. Methods The drug susceptibility of 34 clinical strains of C.albicans to 5 kinds of azole was tested by Kirby-Bauer method. The polymorphism of upc2 gene was analyzed by DNA sequencing, and the m RNA level of cdr1 gene was measured by RT-PCR. The upc2 gene polymorphism and cdr1 m RNA of drug-resistant strains were respectively compared with those of drug-sensitive strains. Results Among the 14 strains of C.albicans with fluconazole resistance, 3 were multi-drug resistant, 6 were dual-drug resistant, and 5 were single-drug resistant, and the rest of 20 were susceptible to all five azole drugs. G1927 A polymorphism of upc2 gene appeared in 5strains fluconazole resistance of candida alicans, but not in 20 fluconazole-sensitive strains. The rate of G1927 A of upc2 gene in fluconazole-resistant C. albicans was 35.7%, significantly higher than that of fluconazole-sensitive strains（χ~2= 8.37,P〈0.01）. The cdr1 m RNA of upc2 gene with G1927 A was much more in multidrug-resistant C. albicans than in dual-drug resistant strains, and the cdr1 m RNA in both was more than that of fluconazole-sensitive strains. Conclusion The G1927 A polymorphism of upc2 gene can cause multi-drug or dual-drug resistance phenotype to azoles in C. albicans by the upregulation of cdr1 gene.

关 键 词：白色念珠菌 upc2基因 cdr1基因 多态性 唑类药物耐药 

分 类 号：R519.3[医药卫生—内科学]