Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India 560012.
IUBMB Life. 2018 Sep;70(9):917-925. doi: 10.1002/iub.1882. Epub 2018 Aug 20.
More than a century has passed since the identification of Mycobacterium tuberculosis (Mtb) as the causative agent of tuberculosis (TB), we still are nowhere close to eradicating this deadly disease. Moreover, emergence of new drug-resistant strains has further complicated the situation, making it even more difficult to treat by conventional therapy regimens. Humans are the only reservoir for the existence and propagation of Mtb, which suggests that its latent forms will be most difficult to eradicate, till the human race lasts. Mtb has been associated with us for ages and its evolution is strictly guided to exploit its human host for survival and spread. The strategies employed by Mtb are unique and host specific, thereby making it hard to break this association without accurate understanding of this host-pathogen interaction. Metabolic pathways have always been at the heart of Mtb pathogenesis, with a continuous cross-talk between the pathogen and the host. Over the years, Mtb has mastered the art of manipulating the host machinery, along with modulating its own metabolism for survival in the hostile conditions. Here we aim to summarize the history of tuberculosis, its pathology and recent advances in basic understanding of the machinery, with eventual gape on the novel therapeutic strategies emerged in the past decade. © 2018 IUBMB Life, 70(9):917-925, 2018.
自 19 世纪发现结核分枝杆菌(Mycobacterium tuberculosis,Mtb)是结核病(tuberculosis,TB)的病原体以来,已经过去了一个多世纪,我们仍然远未实现消除这种致命疾病的目标。此外,新的耐药菌株的出现进一步使情况复杂化,使得传统治疗方案更难治疗。人类是 Mtb 存在和传播的唯一宿主,这表明其潜伏形式将是最难根除的,直到人类灭绝。Mtb 与我们相伴已久,其进化受到严格指导,以利用人类宿主生存和传播。Mtb 采用的策略是独特的和宿主特异性的,因此,如果没有对这种宿主-病原体相互作用的准确理解,就很难打破这种联系。代谢途径一直是 Mtb 发病机制的核心,病原体与宿主之间存在持续的交叉对话。多年来,Mtb 已经掌握了操纵宿主机制的艺术,同时调整自身代谢以在恶劣环境中生存。在这里,我们旨在总结结核病的历史、病理学以及对其发病机制的最新基础理解的进展,并最终着眼于过去十年中出现的新型治疗策略。