MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, United Kingdom.
Department of Mathematics, Imperial College London, London, United Kingdom.
PLoS One. 2018 Jun 19;13(6):e0199316. doi: 10.1371/journal.pone.0199316. eCollection 2018.
Correct chromosomal segregation, coordinated with cell division, is crucial for bacterial survival, but despite extensive studies, the mechanisms underlying this remain incompletely understood in mycobacteria. We report a detailed investigation of the dynamic interactions between ParA and ParB partitioning proteins in Mycobacterium smegmatis using microfluidics and time-lapse fluorescence microscopy to observe both proteins simultaneously. During growth and division, ParB presents as a focused fluorescent spot that subsequently splits in two. One focus moves towards a higher concentration of ParA at the new pole, while the other moves towards the old pole. We show ParB movement is in part an active process that does not rely on passive movement associated with cell growth. In some cells, another round of ParB segregation starts before cell division is complete, consistent with initiation of a second round of chromosome replication. ParA fluorescence distribution correlates with cell size, and in sister cells, the larger cell inherits a local peak of concentrated ParA, while the smaller sister inherits more homogeneously distributed protein. Cells which inherit more ParA grow faster than their sister cell, raising the question of whether inheritance of a local concentration of ParA provides a growth advantage. Alterations in levels of ParA and ParB were also found to disturb cell growth.
正确的染色体分离与细胞分裂相协调,对细菌的生存至关重要,但尽管进行了广泛的研究,分枝杆菌中这一机制仍不完全清楚。我们使用微流控技术和延时荧光显微镜,对分枝杆菌中的 ParA 和 ParB 分隔蛋白的动态相互作用进行了详细研究,以同时观察这两种蛋白。在生长和分裂过程中,ParB 呈现为聚焦的荧光斑点,随后分裂成两个。一个焦点向新极点处 ParA 的高浓度区域移动,而另一个焦点向旧极点移动。我们表明 ParB 的运动部分是一个主动过程,不依赖于与细胞生长相关的被动运动。在一些细胞中,在细胞分裂完成之前,就开始了第二轮 ParB 分隔,这与第二轮染色体复制的启动一致。ParA 荧光分布与细胞大小相关,在姐妹细胞中,较大的细胞继承了局部浓度较高的 ParA 峰,而较小的姐妹细胞则继承了分布更均匀的蛋白质。继承更多 ParA 的细胞比其姐妹细胞生长得更快,这引发了一个问题,即继承局部浓度的 ParA 是否提供了生长优势。还发现 ParA 和 ParB 水平的改变会干扰细胞生长。