热带念珠菌靶位酶基因变异与氟康唑耐药的关系

Relationship between ERG11 gene mutation and resistance of Candida tropicalis to fluconazole

目的探讨热带念珠菌靶位酶(ERG11)基因的改变与氟康唑耐药的相关性。方法根据热带念珠菌ERG11基因序列设计引物,以标准株为对照,对临床分离的耐药株、剂量依赖株(S-DD)和敏感株进行靶位酶ERG11基因PCR扩增,测序之后比对分析标准株,耐药株、剂量依赖株和敏感株的序列差异,分析靶位酶基因改变与氟康唑耐药的相关性。结果热带假丝酵母氟康唑敏感株与敏感标准株序列一致;而S-DD株中出现T783C和G1362A沉默突变;耐药株中出现碱基序列T225C、C461T、G1362A等3种突变点,并导致丝氨酸(S)154苯丙氨酸(F)氨基酸突变。结论热带念珠菌靶位酶ERG11基因氨基酸序列的突变与氟康唑耐药有一定的相关性。

Objective To investigate the relationship between Gt-ERG11 gene mutation and the resistance of Candida tropicalis to fluconazole. MethOdS Ct-ERGll genes from standard strain, sensitive strains, S-DD strains and resistance strain of Candida tropiealis were amplified by PCR, and the nucleotide sequences were analyzed to detect the relationship about Ct-ERG1 lgene mutation and resistance to fluconazole. Result Three fluconazole-susceptible strains were completely identical with the standard stains, while two silent mutations T783C and G1362A were detected in two fluconazole S-DD strains and three nucleotide substitutions of T225C,C461T and G1362A were found in fluconazole resistant strain which resulted in sient mutation of S154F. Conclusion The missense mutation in Ct-ERG11 gene is associated with resistance of Caudida tropJcalis to fluconazole.