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白念珠菌人工诱导耐药株唑靶酶三磷酸鸟苷环水解酶Ⅰ功能区的序列分析

Cloning and sequencing of the GTP cyclohydrolaseⅠfunction region of azole target enzyme gene in artificially induced resistant Candida albicans

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【作者】 邓旭亮张新成张锋李若瑜陆慧君贺文琦刘立国范彬胡晓阳

【Author】 DENG Xu-liang1, ZHANG Xin-cheng2, ZHANG Feng3,LI Ruo-yu4, LU Hui-jun2, HE Wen-qi2, LIU Li-guo2, FAN Bin1,HU Xiao-yang 1△ (1. Peking University School and Hospital of Stomatology, Beijing 100081, China ; 2. College of Animal Science and Veterinary Medicine, Jilin University; 3. The 2nd Hospital of Beijing Armed Police Force;4.Peking University First Hospital)

【机构】 北京大学口腔医学院·口腔医院吉林大学畜牧兽医学院北京武警总队第二医院北京大学第一医院北京大学口腔医学院·口腔医院 北京100081北京100081

【摘要】 目的:研究羊毛甾醇14α脱甲基酶(14DM)DNA序列中三磷酸鸟苷(GTP)环水解酶Ⅰ功能区域基因突变与白念珠菌对氟康唑耐药性的关系。方法:体外采用氟康唑结合阿苯达唑进行人工耐药性诱导1株白念珠菌标准菌株和2株临床分离对氟康唑敏感株,将获得的3株人工诱导耐药白念菌株和另外2株临床分离对氟康唑耐药的白念菌株,通过PCR扩增目的片段,并克隆到pMD18T载体上,测序分析诱导前后基因序列碱基变化。结果:经体外人工耐药性诱导后,标准白念珠菌菌株和临床分离敏感白念珠菌菌株GTP环水解酶Ⅰ功能区域多处碱基突变,部分碱基变化引起了氨基酸的改变,与临床分离耐药白念珠菌在碱基变化及其导致的编码氨基酸变化相似。结论:14DMGTP环水解酶Ⅰ功能区域基因突变与白念珠菌的耐药性有相关性。

【Abstract】 Objective: To study the relationship between gene mutation of GTP cyclohydrolase I function region in lanosterine 14 α-demethylase (14-DM) DNA sequence and drug resistance of Candida albicans. Methods: One standard strain and 2 isolate strains of Candida albicans were induced artificially by fluconazole plus albendazole. The gene fragments of the 3 strains and another 2 clinical isolates which were resistant to fluconazol were detected by PCR, and then cloned onto pMD-18T vectors to sequence and analyze the change of gene sequence after the induction. Results: The sequences underwent substantial gene mutations after induction. Some of the mutations resulted in alteration of amino acids. The sequence change and subsequent alteration of amino acids in the tested strains coincided with those in the clinical isolates. Conclusion: Gene mutation and alteration of amino acid of 14-DM GTP domain are related to azole-resistance in Candida albicans.

【基金】 国家自然科学基金(30300384)资助~~
  • 【文献出处】 北京大学学报(医学版) ,Journal of Peking University(Health Sciences) , 编辑部邮箱 ,2006年03期
  • 【分类号】R379.4
  • 【下载频次】138
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