过氧化氢酶活性KatG基因与结核分支杆菌异烟肼耐药性的相关性研究

Relationship between catalase activity, KatG gene and isoniazid resistance in M.tuberculosis

目的探讨过氧化氢酶活性、ＫａｔＧ基因及其突变与结核分支杆菌异烟肼（ＩＮＨ）耐药性的相关关系。方法对５８株结核分支杆菌临床分离株进行过氧化氢酶活性测定，并采用聚合酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）方法进一步分析结核分支杆菌中ＫａｔＧ基因及其突变的情况。结果所有２６株敏感菌均有ＫａｔＧ基因及过氧化氢酶的表达；３２株耐药菌中，８株（２５％）缺乏过氧化氢酶活性，３株（１０％）ＫａｔＧ基因完全缺失，且主要发生于高度耐药菌中。进一步对８株耐药菌进行ＰＣＲ－ＳＳ－ＣＰ分析，发现均存在ＫａｔＧ基因突变。结论过氧化氢酶活性缺乏及ＫａｔＧ基因的完全缺失主要与ＩＮＨ高度耐药性有关。

Objective To investigate the relationship between catalase activity, KatG gene, gene mutation and INH resistance in M.tuberculosis.Method Catalase activities in 58 M.tuberculosis isolates were tested, and KatG gene mutations were detected futher by PCR SSCP. Result None of INH sensitive isolates lacked KatG sequences and all expressed catalase. 8(25%) INH resistant isolates did not express catalase and 3(10%) lacked KatG gene, most of which were strains of high levels of resistance (MIC>50 μg/ml). 8 INH resistant isolates were analyzed futher by PCR SSCP and all were found to have KatG gene mutation. Conclusion These findings indicated that lacking of catalase activity and KatG gene deletion occured mainly in those highly INH resistant strains, gene mutation other than complete deletion of KatG gene may be the major mechanism of INH resistance.