Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
Mech Ageing Dev. 2012 Apr;133(4):138-46. doi: 10.1016/j.mad.2011.09.003. Epub 2011 Oct 1.
About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages.
据估计，大约有三分之一的人口感染了结核分枝杆菌。耐药菌株的出现和长期的治疗策略迫使科学界寻找新的药物靶点，并开发新的疫苗。在宿主巨噬细胞中，细菌在富含活性氮和氧物种的环境中生存，这些物质能够破坏其基因组。因此，为了在宿主中成功生存，病原体必须具有强大的 DNA 修复机制。结核分枝杆菌基因组序列分析表明，它缺乏错配修复途径，这表明其他 DNA 修复途径（如核苷酸切除修复和碱基切除修复途径）的作用更大。本文总结了涉及分枝杆菌这两种修复途径的研究结果，主要集中在我们自己的研究成果上。我们使用耻垢分枝杆菌模型的研究结果表明，单一或多种 DNA 修复功能的缺失严重损害了它们的 DNA 修复能力，并在巨噬细胞中常见的条件下削弱了它们的生长。
