Priestman Miles, Thomas Philipp, Robertson Brian D, Shahrezaei Vahid
Department of Medicine, MRC Centre for Molecular Bacteriology and Infection, Imperial College LondonLondon, United Kingdom.
Department of Mathematics, Imperial College LondonLondon, United Kingdom.
Front Cell Dev Biol. 2017 Jul 12;5:64. doi: 10.3389/fcell.2017.00064. eCollection 2017.
The decision to divide is the most important one that any cell must make. Recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. Mycobacteria, including the causative agent of tuberculosis , are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. The interplay between asymmetric cell division and adder size control has not been extensively investigated. Moreover, the impact of changes in the environment on growth rate and cell size control have not been addressed for mycobacteria. Here, we utilize time-lapse microscopy coupled with microfluidics to track live cells as they grow and divide over multiple generations, under a variety of growth conditions. We demonstrate that, under optimal conditions, cells robustly follow the adder principle, with constant added length per generation independent of birth size, growth rate, and inherited pole age. However, the nature of the carbon source induces deviations from the adder model in a manner that is dependent on pole age. Understanding how mycobacteria maintain cell size homoeostasis may provide crucial targets for the development of drugs for the treatment of tuberculosis, which remains a leading cause of global mortality.
细胞分裂的决定是任何细胞都必须做出的最重要的决定。最近的单细胞研究表明，大多数细菌遵循细胞大小控制的“加法器”模型，在分裂前整合固定量的细胞壁材料。包括结核病病原体在内的分枝杆菌已知会进行不对称分裂，导致子细胞在生长速率、倍增时间和其他生长特性方面存在异质性。不对称细胞分裂与加法器大小控制之间的相互作用尚未得到广泛研究。此外，环境变化对分枝杆菌生长速率和细胞大小控制的影响也未得到探讨。在这里，我们利用延时显微镜结合微流控技术，在多种生长条件下跟踪活细胞多代生长和分裂的过程。我们证明，在最佳条件下，细胞严格遵循加法器原则，每一代增加的长度恒定，与出生大小、生长速率和遗传极龄无关。然而，碳源的性质会以一种依赖于极龄的方式导致与加法器模型的偏差。了解分枝杆菌如何维持细胞大小稳态可能为开发治疗结核病的药物提供关键靶点，结核病仍是全球死亡的主要原因。
