白念珠菌临床分离株吡咯类耐药机制研究

发布时间：2018-05-30 11:41

本文选题：外阴阴道念珠菌病 + 白念珠菌　；参考：《中国感染与化疗杂志》2017年04期

【摘要】：目的分析女性生殖道感染白念珠菌临床分离株对5种抗真菌药物的耐药率,探讨白念珠菌对吡咯类药物的耐药机制。方法 (1)收集2015年1-12月自复旦大学附属妇产科医院女性生殖道感染患者中分离的白念珠菌1 646株,统计菌株对5种抗真菌药物的耐药情况。(2)收集包括该院和上海市另2所妇产科专科医院微生物室临床分离白念珠菌氟康唑耐药菌株30株、剂量依赖性敏感(S-DD)菌株13株、敏感菌株10株。采用实时荧光定量PCR技术分析吡咯类耐药组、S-DD组和敏感组之间药物外排泵相关基因CDR1、CDR2、MDR1和药物靶酶基因ERG11表达水平的差异。同时,PCR扩增ERG11和ERG3基因并测序,分析ERG11和ERG3基因与耐药相关的突变位点。结果 (1)1 646株白念珠菌对伊曲康唑耐药率最高,为5.2%,对伏立康唑、氟康唑和5-氟胞嘧啶的耐药率分别为3.2%、2.5%和2.1%,所有菌株对两性霉素B均敏感。(2)S-DD组和耐药组ERG11基因表达较敏感组均显著升高,差异有统计学意义(P0.05);而药物外排泵基因CDR1、CDR2和MDR1表达量在敏感组、S-DD组和耐药组间差异无统计学意义。(3)检测到ERG11基因存在13个错义突变位点,其中T123I、P98S和Y286D为新发现的3个氨基酸置换位点;且T123I和Y132H同时出现在26株耐药株中,其中16株为吡咯类药物全耐药;此外,2株吡咯类全耐药菌株中检测到ERG3基因杂合突变。结论外阴阴道念珠菌病患者中分离的白念珠菌对吡咯类药物的耐药率比5-氟胞嘧啶和两性霉素高;ERG11基因突变及其过表达是该病白念珠菌吡咯类耐药的主要分子机制之一。
[Abstract]:Objective to analyze the resistance rate of Candida albicans isolates from female reproductive tract to 5 antifungal drugs and to explore the mechanism of drug resistance of Candida albicans to pyrrole drugs. Methods (1) 1646 strains of Candida albicans isolated from female genital tract infection in the affiliated obstetrics and Gynecology Hospital of Fudan University in 2015 were collected, and 5 kinds of anti true strains were collected. (2) collect 30 strains of fluconazole resistant strains of Candida albicans, 13 strains of dose dependent (S-DD) strain and 10 sensitive strains, including 30 strains of Candida albicans in the microorganism room of the 2 Department of gynecology and obstetrics, Shanghai. The difference in the expression level of the pump related genes CDR1, CDR2, MDR1 and drug target gene ERG11. At the same time, PCR amplified ERG11 and ERG3 genes and sequencing, and analyzed the mutation sites associated with ERG11 and ERG3 genes. Results (1) the resistance rate of 1646 Candida albicans to itraconazole was the highest, 5.2%, and the resistance to voriconazole, fluconazole and 5- fluorcytosine. The rates were 3.2%, 2.5% and 2.1% respectively. All the strains were sensitive to amphotericin B. (2) the ERG11 gene expression in the S-DD group and the drug resistant group increased significantly, and the difference was statistically significant (P0.05), but the expression of CDR1, CDR2 and MDR1 in the drug efflux pump gene was not statistically significant in the sensitive group, in the S-DD group and in the drug resistant group. (3) the ERG11 gene was detected. There were 13 missense mutation sites, of which T123I, P98S and Y286D were newly found 3 amino acid replacement sites, and T123I and Y132H appeared at the same time in 26 resistant strains, 16 of them were all resistant to pyrrole. In addition, 2 strains of pyrrole all resistance strains detected the heterozygous mutation of the ERG3 gene. The resistance rate of Candida albicans to pyrrole is higher than that of 5- fluorocytosine and amphotericin, and the mutation and overexpression of ERG11 gene are one of the main molecular mechanisms of Candida albicans resistance to pyrrole.
【作者单位】：复旦大学附属妇产科医院检验科;
【分类号】：R446.5;R711.3

【相似文献】