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目的:探讨分离自艾滋病患者的白念珠菌唑类药物耐药株中Erg11基因的突变及其与唑类耐药的关系。方法:分离自艾滋病患者的100株真菌标本,经科玛嘉显色培养鉴定为白念珠菌85株,根据美国临床实验室标准化协会制订的M27-A方案的液体微量稀释法行体外药物敏感试验,共鉴定出27株唑类耐药株(耐氟康唑和/或伊曲康唑和/或伏立康唑)。27株耐药株提取基因组DNA后,对其Erg11基因行PCR扩增、测序并与Genebank中敏感株进行比对分析。结果:在27株唑类耐药株中共发现25处不同点突变,其中5处引起氨基酸替换,分别为D116E、E266D、H485T、V447I和V488I,27株均发生H485T突变,7株耐药株发生E266D突变,4株耐药株发生V488I突变,其中1株同时发生E266D和V488I突变,1株发生V447I突变。结论:分离自艾滋病患者的白念珠菌唑类耐药株中Erg11基因的突变热变区和有意义突变与分离自其他宿主的唑类耐药株的突变情况基本一致;分离自艾滋病患者的白念珠菌唑类耐药株Erg11基因突变并非唯一致耐药因素。
Objective: To investigate the mutation of Erg11 gene in Candida albicans resistant strains isolated from AIDS patients and its relationship with azole resistance. Methods: 100 strains of fungi isolated from AIDS patients were identified as Candida albicans by Komaga color culture. According to the M27-A protocol of liquid microdilution developed by the American Society of Clinical Laboratory Standards, in vitro drug sensitivity test A total of 27 azole resistant strains (fluconazole-resistant and / or itraconazole and / or voriconazole) were identified. After the genomic DNA was extracted from 27 resistant strains, the Erg11 gene was amplified by PCR, sequenced and compared with the sensitive strains in Genebank. Results: A total of 25 different point mutations were found in 27 strains of azole resistant strains. Among them, amino acid substitutions were induced in 5 sites, which were D116E, E266D, H485T, V447I and V488I, 27 H485T mutations and 7 resistant strains E266D mutation, four strains of drug-resistant V488I mutation occurred, including a simultaneous E266D and V488I mutation, a mutation occurred V447I. CONCLUSIONS: Mutations in the mutant Erg11 gene in Candida albicans isolates from AIDS patients with mutations and meaningful mutations are nearly identical to those from azole-resistant isolates from other hosts. The mutation of Erg11 gene in Candida-azole-resistant strains is not the only drug-resistant factor.