白念珠菌ERG11基因突变与氟康唑耐药性的关系  

The relationship between ERG11 gene mutation of Candida albicans and fluconazole-resistance

作　　者：苏逸丹[1] 汪师贞[2] 翁心华[3] 王家俊[3] 章强强[3] 张永信[3] 朱琪泉 

机构地区：[1]新疆医科大学第二附属医院,乌鲁木齐830028 [2]新疆医科大学第一附属医院,乌鲁木齐830054 [3]上海医科大学华山医院,上海200040 [4]复旦大学遗传研究所,上海200043

出　　处：《中国抗生素杂志》2000年第6期467-470,共4页Chinese Journal of Antibiotics

摘　　要：探讨白念珠菌氟康唑作用的靶酶编码基因 (ERG11)突变与耐药性的关系。分离抽提分别对氟康唑敏感和耐药的白念珠菌基因组 DNA,根据 ERG11编码序列设计一对上下游引物 ,对靶酶活性中心血色素结合区和疏水端螺旋区的基因表达序列进行 PCR扩增 ,经 DNA测序比较敏感和耐药菌株的碱基差异。结果 :6株氟康唑耐药白念珠菌此段序列有 5个位点发生突变 ,其中 5株第 1344 bp位点 G→A的突变致所编码的第 44 8个氨基酸由甘氨酸 (G)变为谷氨酸 (E)。结论 :ERG11基因突变致所编码的氨基酸改变与氟康唑耐药有关。To explore the relationship between fluconazole resistance and mutations of ERG11 gene encoding cytochrome P450 lanosterol 14α demethylase (P450 14DM), the target of azole drugs. The genomic DNA of fluconazole susceptible and resistant Candida albicans isolates were extracted, DNA fragments encoding for the P450 14DM′s heme biding domain and hydrophobic stretch were amplyfied by PCR and DNA differences of these fragments were compared by DNA sequencing. Results: There were 5 base mutations at the position of 996bp, 1140bp, 1203bp, 1296bp and 1344bp in 6 fluconazole resistant isolates respectively and 5 of 6 strains occurred G→A base mutation at the position 1344, which could result a single amino acid substitution (G448E). Conclusion: It is likely to suggest the relationship of the gene mutations of ERG11 effect on the amino acid sequence and the fluconazole resistance.

关 键 词：白念珠菌 基因突变 氟康唑 耐药性 抗真菌药 

分 类 号：R978.5[医药卫生—药品] R379.4[医药卫生—药学]