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异烟肼耐药和敏感结核分枝杆菌的比较蛋白质组学研究

Comparison of the proteome of Mycobacterium tuberculosis isoniazid susceptible strain with isoniazid resistant strain

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【作者】 乐军刘丽蓉谢建平刘蓓梁莉王洪海

【Author】 YUE Jun * , LIU Li-rong, XIE Jian-ping, LIU Bei, LIANG Li, WANG Hong-hai. *State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China

【机构】 复旦大学生命科学学院遗传学研究所复旦大学生命科学学院遗传学研究所上海市肺科医院复旦大学生命科学学院遗传学研究所 上海市肺科医院200433上海

【摘要】 目的 研究结核分枝杆菌异烟肼耐药菌株与敏感菌株的蛋白质表达差异 ,鉴定结核分枝杆菌中与异烟肼耐药相关的菌体蛋白。方法 应用双向电泳技术比较 2株异烟肼耐药菌株与 2株敏感菌株的全菌蛋白表达图谱差异 ,发现异烟肼耐药结核分枝杆菌表达量显著增加 2 6个蛋白质斑点 ,通过基质辅助激光解吸 /电离飞行时间质谱仪进行质谱分析 ,获得 6个明确的肽质量指纹谱 ,通过蛋白质数据库进行检索分析。结果  6个蛋白分别为海藻糖磷酸磷酸酶、铁钼蛋白A、莽草酸 5脱氢酶、葡萄糖胺果糖 6磷酸氨基转移酶、吲哚 3甘油磷酸合成酶、TetR家族转录调控因子。结论 上述蛋白的鉴定将对发现新型抗结核药物靶位和异烟肼耐药结核病诊断的分子标志物可能有所裨益

【Abstract】 Objective To compare the proteome of isoniazid(INH)-resistant M. tuberculosis with that of sensitive strains for identifing unique proteins of these strains. Methods The two-dimensional electrophoresis(2-DE) were used to compare the global protein patterns between INH-resistant and INH-sensitive strains. Protein spots remarkly increased in INH-resistant strains, which were digested in gel by enzyme and the mass of generated peptides were measured by matrix assisted laser desorption ionization time of flight mass spectrometry( MALDI-TOF-MS). The data obtained from peptide mass fingerprinting were used in protein database search. Results Six spots of proteins in gel were identified as trehalose-6-phosphate phosphatase, moaA, shikimate 5-dehydrogenase, glucosamine-fructose-6-phosphate aminotransferase, indole-3-glycerol phosphate synthase and TetR-family transcriptional regulator. Conclusion These proteins are potentially target sites for chemotherapy against M. tuberculosis and new marker in the detection of resistance of M. tuberculosis .

【基金】 国家十五科技攻关项目 (2 0 0 1BA70 5B0 3 )
  • 【文献出处】 中华微生物学和免疫学杂志 ,Chinese Journal of Microbiology and Immunology , 编辑部邮箱 ,2004年04期
  • 【分类号】R378
  • 【被引频次】59
  • 【下载频次】756
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