Pathogen Molecular Biology Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
TB Centre, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Nucleic Acids Res. 2018 Aug 21;46(14):6950-6961. doi: 10.1093/nar/gky574.
Protein synthesis is a fundamental requirement of all cells for survival and replication. To date, vast numbers of genetic and biochemical studies have been performed to address the mechanisms of translation and its regulation in Escherichia coli, but only a limited number of studies have investigated these processes in other bacteria, particularly in slow growing bacteria like Mycobacterium tuberculosis, the causative agent of human tuberculosis. In this Review, we highlight important differences in the translational machinery of M. tuberculosis compared with E. coli, specifically the presence of two additional proteins and subunit stabilizing elements such as the B9 bridge. We also consider the role of leaderless translation in the ability of M. tuberculosis to establish latent infection and look at the experimental evidence that translational regulatory mechanisms operate in mycobacteria during stress adaptation, particularly focussing on differences in toxin-antitoxin systems between E. coli and M. tuberculosis and on the role of tuneable translational fidelity in conferring phenotypic antibiotic resistance. Finally, we consider the implications of these differences in the context of the biological adaptation of M. tuberculosis and discuss how these regulatory mechanisms could aid in the development of novel therapeutics for tuberculosis.
蛋白质合成是所有细胞生存和复制的基本要求。迄今为止，已经进行了大量的遗传和生化研究来探讨翻译的机制及其在大肠杆菌中的调控，但只有少数研究调查了其他细菌中的这些过程，特别是在像结核分枝杆菌这样的生长缓慢的细菌中，结核分枝杆菌是人类结核病的病原体。在这篇综述中，我们强调了结核分枝杆菌与大肠杆菌在翻译机制方面的重要差异，特别是存在两种额外的蛋白质和亚基稳定元件，如 B9 桥。我们还考虑了无领导者翻译在结核分枝杆菌建立潜伏感染能力中的作用，并研究了在应激适应过程中翻译调节机制在分枝杆菌中起作用的实验证据，特别是关注大肠杆菌和结核分枝杆菌之间毒素-抗毒素系统的差异，以及可调谐翻译保真度在赋予表型抗生素耐药性中的作用。最后，我们根据结核分枝杆菌的生物学适应性来考虑这些差异的影响，并讨论这些调节机制如何有助于开发结核病的新型治疗方法。
