A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization
Department of Microbiology and Physiological Systems; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Microbiology | Molecular Biology
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 [1-3]. Mycobacteria elongate and divide asymmetrically, giving rise to significant variation in cell size and elongation rate among closely related cells [4, 5]. 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 [1, 2, 6-8]. 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-Guerin (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 cell-cycle timing in both slow and fast growth conditions, we found that well-studied models of cell-size control 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.
DOI of Published Version
Curr Biol. 2017 Nov 6;27(21):3367-3374.e7. doi: 10.1016/j.cub.2017.09.046. Epub 2017 Oct 26. Link to article on publisher's site
Current biology : CB
Logsdon, Michelle M.; Ho, Po-Yi; Papavinasasundaram, Kadamba; Richardson, Kirill; Cokol, Murat; Sassetti, Christopher M.; Amir, Ariel; and Aldridge, Bree B., "A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization" (2017). UMass Metabolic Network Publications. 147.