女性生殖道白色念珠菌唑类药物耐药转录因子编码基因UPC2的多态性研究

Polymorphisms of azole resistant gene UPC2 in Candida albicans from female genital tract

目的研究调控白色念珠菌耐唑类药的锌簇转录因子编码基因UPC2的单核苷酸多态性,为防治其耐药提供依据。方法采用酵母菌药敏条测定分离自女性生殖道的白色念珠菌的药物敏感性,收集唑类耐药株,提取基因组DNA,PCR法检测白色念珠菌UPC2,扩增产物测序后,通过Vector NTI进行单核苷酸多态性分析。结果从1 426株白色念珠菌中共分离到54株唑类药物耐药的菌株,在这54株耐药株中,有29株发生UPC2基因的突变,而其余的25株没有发生突变。在这些UPC2突变株中,得到了3种单个氨基酸取代的不同突变:G377S、W493L、G648S。结论在白色念珠菌耐药株中检测到UPC2的单核苷酸多态性,而在敏感株中则否,提示UPC2核苷酸序列点突变机制可能参与白色念珠菌耐唑类药物的调控。

Objective To study the polymorphism of the zinc cluster transcription factor encoding gene UPC2,which regulates the azole resistance of Candida albicans,so as to provide laboratory evidence for the prevention and treatment of drug resistance of Candida albicans.Methods The drug susceptibility of Candida albicans isolated from female genital tract was determined by Yeast drug sensitive strip.The azole-resistant strains were collected.The genomic DNA of fungi was extracted.The UPC2 of azole-resistant Candida albicans was detected by PCR.The amplified products were sequenced and analyzed by Vector NTI.Results A total of 1 426 strains of Candida albicans were isolated,of which 54 were azole-resistant Candida albicans.Of those 54 isolates,29 contained a mutation in UPC2,whereas the remaining 25 isolates did not.Among the isolates containing mutations in UPC2,we recovered three distinct mutations resulting in putative single amino acid substitutions:G377 S,W493 L and G648 S.Conclusion Polymorphism of UPC2 gene was detected in resistant strains of Candida albicans,but not in susceptible strains,suggesting that point mutation of UPC2 gene may be involved in the regulation of azole resistance in Candida albicans.