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异烟肼(INH)是主要抗结核药物之一。耐INH 的临床分离株表现为过氧化氢酶活性降低和对豚鼠毒力的相对缺失。为此,研究了分支杆菌对INH 耐药的分子遗传学基础。方法和结果分离耻(耳后)分支杆菌突变株BH1(高度耐药,能在500μg/mL INH 中生长),用含具有结核分支杆菌(结核菌,H_(37)Rv 株)DNA 特征插入片段的穿梭质粒克隆转化。其转化物之一pBH4表现为INH 超敏感,最低抑菌浓度(MIC)为8μg/mL,过氧化氢酶活性
Isoniazid (INH) is one of the major anti-TB drugs. INH-resistant clinical isolates showed decreased catalase activity and relative loss of virulence to guinea pigs. Therefore, the molecular genetic basis of mycobacterial resistance to INH was studied. Methods and Results Bacillus subtilis mutants BH1 (highly resistant, capable of growth in 500 μg / mL INH) were isolated and inserted into a DNA fragment containing Mycobacterium tuberculosis (Mycobacterium tuberculosis, H_ (37) Rv strain) Shuttle plasmid cloning transformation. One of its transformants pBH4 showed INH hypersensitivity, the minimum inhibitory concentration (MIC) of 8μg / mL, catalase activity