阴道白假丝酵母菌的耐药性和ERG11基因突变关系研究

Research on the relationship between the mutations of ERG11 gene and the resistance of pyrrolic antifungal agents in vaginal candida albicans

目的探讨ERG11基因突变与白假丝酵母菌对吡咯类药物敏感性下降的关系。方法收集VVC患者的白假丝酵母菌60株,用科玛嘉念珠菌显色培养基作菌种鉴定,纸片扩散法进行药敏试验,选取所有中度敏感株和耐药株用聚合酶链反应扩增(PCR)ERG11基因,将PCR产物进行测序分析和比对分析。结果 60株白假丝酵母菌对咪康唑、酮康唑和氟康唑敏感率分别为36.7%、56.1%和80%;将38株中度敏感株和耐药株进行ERG11基因分析后共发现29个有义突变和25个同义突变,其中,有义突变中发现多个新突变位点。结论有些新发现的突变位点可能与耐药相关;多位点有义突变可能降低菌株对药物的敏感性。

Objective To invesigate the relationship between mutation of ERGll gene and the decreased sensitivity to pyrrolic antifungal agents in vaginal Cartdida albicans. Methods sixty strains of Candida albicans from VVC patients were collected and identified by CHROM agar. The drug resistance was detected by disk diffusion method. The ERGll gene of the moderately susceptible and resistant strains was amplified by PCR. The PCR products were analyzed by DNA sequencing. Results The sensitive rates of sixty strains of Candida albicans strains to miconazole, ketoconazole and fluconazole were 36.7%, 56.1% and 80%, respectively. After comparison of ERGll gene DNA sequences alignment, we found 29 missense mutations and 25 silent mutations in 38 strains of moderately susceptible and resistant strains. Several new mutations were found in ERGll genein the missense mutations. Conclusion Some new mutations were found in ERGll gene which might be associated with drug resistance. Multiple amino acid substitutions in Ergll of vaginal Candida albicans may reduce the sensitivity to pyrrolic antifungal agents.