耐氟康唑光滑念珠菌ERG11基因突变分析  

Analysis of ERG11 gene mutations in fluconazole-resistant Candida glabrata strains

作　　者：沈银忠[1] 卢洪洲[2] 张永信[2] 

机构地区：[1]上海市公共卫生临床中心感染一科,201508 [2]复旦大学附属华山医院感染科

出　　处：《中华传染病杂志》2010年第6期331-335,共5页Chinese Journal of Infectious Diseases

基　　金：上海市卫生局青年科研项目（2008Y030）;“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项（2009ZX10003-017）

摘　　要：目的 分析耐药氟康唑光滑念珠菌ERG11基因突变情况,探讨ERG11基因突变在光滑念珠菌耐药性形成中的作用.方法 分别将氟康唑耐药光滑念珠菌株9株和敏感株10株的ERG11基因克隆至pUC57-T载体,利用载体上的通用引物对其ERG11基因整个开放读码框进行双向测序,将测序结果与网上公布的标准序列进行比对.结果 19株光滑念珠菌耐药株和敏感株ERG11基因共存在10个点突变,均为同义突变,无错义突变和移码突变.其中5个点突变在耐药株和敏感株中均出现,3个只出现在耐药株,2个只出现在敏感株.点突变主要位于ERG11基因1320～2200 bp,出现频率最高的3个点突变为T2117A、A1583G、T1328C.结论 光滑念珠菌ERG11基因序列存在多态性,未发现因ERG11基因突变引起靶酶氨基酸改变而导致的光滑念珠菌对氟康唑耐药.Objective To study the mutations of ERG11 gene which encodes P450 lanosterol 14-α demethylase, and to explore the possible role of ERG11 gene in inducing fluconazole resistance in Candida glabrata. Methods ERG11 genes of 9 fluconazole-resistant Candida glabrata isolates and 10 fluconazole-sensitive Candida glabrata isolates were cloned into pUC57-T vector. The open reading frame of ERG11 gene were sequenced by two directional sequencing using universal primers. All sequences were compared with the published sequence. Results Ten kinds of synonymous point mutation were found. Neither missense mutation nor frame-shifting mutation was found. Among the 10 kinds of synonymous point mutation, 5 were found in both fluconazole-resistant and fluconazolesensitive Candida glabrata isolates, and 3 were only found in fluconazole-resistant isolates, 2 were only found in fluconazole-sensitive ones. The majority of the point mutations were located between 1320-2200 base pair of ERG11 gene. Conclusions There are ERG11 gene polymorphisms in clinical strains of Candida glabrata. ERG11 gene mutations are not found to be involved in the development of fluconazole resistance in Candida glabrata.

关 键 词：念珠菌 光滑 氟康唑 抗药性 细菌 ERG11基因 真菌 突变 遗传密码 

分 类 号：R446.5[医药卫生—诊断学]