念珠菌耐药相关基因研究

MOLECULAR MECHANISMS OF RESISTANCE TO FLUCONAZOLE IN CANDIDA TROPICALIS CLINICAL STRAINS

目的研究耐氟康唑热带念珠菌临床株Fc 30的基因突变耐药机制。方法对氟康唑靶酶基因erg 11进行PCR扩增,DNA测序,对比分析临床耐药株与敏感株及标准株的靶酶基因DNA序列,确定耐药株基因一级结构上的突变点,并推测分析靶酶蛋白的氨基酸改变及与氟康唑耐药的相关性。结果氟康唑敏感株Fc 17的erg 11基因DNA序列与氟康唑敏感标准菌ATCC750完全一致,耐药株Fc 30出现+225、+264、+395、+461、+513处点突变,导致132、154位氨基酸突变。结论与敏感株相比,耐氟康唑热带念珠菌Fc30 erg11基因出现Y132F耐药相关突变。

Objective To study the mutation mechanisms of resistance to fluconazole in genes of Candida tropicalis clinical strain（Fc 30）. Methods Erg 11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations related to fluconazole resistance. Results The nuclcotide sequence of erg 11 gene of fluconazole-susceptible strain （Fc 17） was completely identical with a reported sequence from a fluconazole- susceptible strain （C.tropicalis ATCC 750）; Five nucleotide substitutions at ＋ 225, ＋ 264, ＋ 395, ＋ 461, ＋ 513 points, resulting in two amino acid mutation changes were identified in the fluconazole- resistant strain（ Fc 30）. Conclusion The erg 11 gene of C, tropicalis Fc 30 was found to have an alteration of Y132F in fluconazole resistance.