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结核病仍是全球最致命的传染病之一,是一个主要的公共健康问题。虽然异烟肼(INH)是用于治疗结核病的主要药物,但长期治疗中INH耐药是有效抗结核病化疗中的一个重要问题。INH是由分枝杆菌酶KatG激活的前药。该研究发现,分枝杆菌DNA结合蛋白1(MDP1)是一个保守的分枝杆菌组蛋白样蛋白,负性调节katG基因转录,导致分枝杆菌对INH表型耐药。MDP1缺陷的包皮垢分枝杆菌与野生型菌株相比,基因表达上调,并增强激活。在包皮垢分枝杆菌中,表达增加出现在静止期,并在生
Tuberculosis is still one of the most deadly infectious diseases in the world and is a major public health problem. Although isoniazid (INH) is the primary drug used to treat tuberculosis, INH resistance is an important issue in the long-term treatment of anti-TB chemotherapy. INH is a prodrug activated by mycobacterial enzyme KatG. The study found that mycobacterial DNA-binding protein 1 (MDP1) is a conserved Mycobacterium histone-like protein that negatively regulates katG gene transcription, resulting in mycobacterial resistance to INH phenotype. MDP1-deficient Mycobacterium smegmatis is up-regulated in gene expression and enhances activation compared to the wild-type strain. In M. smegmatis, increased expression occurs at quiescence and is alive