A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization.
A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization.
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DOI:
10.1016/j.cub.2017.09.046
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发表时间:
2017-11-06
期刊:
影响因子:
--
通讯作者:
Aldridge BB
中科院分区:
文献类型:
--
作者:
Logsdon MM;Ho PY;Papavinasasundaram K;Richardson K;Cokol M;Sassetti CM;Amir A;Aldridge BB
In model bacteria, such as E. coli and B. subtilis, regulation of cell cycle progression and cellular organization achieves consistency in cell size, replication dynamics, and chromosome positioning. Mycobacteria elongate and divide asymmetrically, giving rise to significant variation in cell size and elongation rate among closely related cells. Given the physical asymmetry of mycobacteria, the models that describe coordination of cellular organization and cell cycle progression in model bacteria are not directly translatable. Here we used time-lapse microscopy and fluorescent reporters of DNA replication and chromosome positioning to examine the coordination of growth, division, and chromosome dynamics at a single-cell level in Mycobacterium smegmatis (M. smegmatis) and Mycobacterium bovis Bacillus Calmette–Guérin (BCG). By analyzing chromosome and replisome localization, we demonstrated that chromosome positioning is asymmetric and proportional to cell size. Furthermore, we found that cellular asymmetry is maintained throughout the cell cycle and is not established at division. Using measurements and stochastic modeling of mycobacterial cell size and cycle timing in both slow and fast growth conditions, we found that well-studied cell size control models are insufficient to explain the mycobacterial cell cycle. Instead, we showed that mycobacterial cell cycle progression is regulated by an unprecedented mechanism involving parallel adders (i.e. constant growth increments) that start at replication initiation. Together, these adders enable mycobacterial populations to regulate cell size, growth, and heterogeneity in the face of varying environments. Logsdon et al. study cell cycle dynamics of asymmetrically growing mycobacteria and show how cell cycle, chromosome organization, and division are coordinated in single cells. A parallel adder model, where cells add a constant length between initiations and initiation to division, describes cell size control in M. smegmatis and BCG.
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