Manipulating the Bacterial Cell Cycle and Cell Size by Titrating the Expression of Ribonucleotide Reductase

Zhu, Manlu; Dai, Xiongfeng; Guo, Weilun; Ge, Zengxiang; Yang, Minghan; Wang, Haikuan; Wang, Yiping

doi:10.1128/mbio.01741-17

Cited by 29 publications

(35 citation statements)

References 27 publications

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“…Additionally, studies in bacteria and yeast established that increased dNTP pools can accelerate progression through S phase. We thus hypothesized that a similar mechanism might affect the duration of interphases during the cleavage divisions and, consequently, lead to the overall reduction of accumulated zygotic transcripts [18,19]. Consistent with this idea, we found that when the overall transcriptional output was divided by the period of active transcription, the outputs of embryos with high dNTP concentrations became statistically indistinguishable from control embryos ( Figures S2D-S2F).…”

Section: Resultssupporting

confidence: 76%

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

et al. 2019

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In BriefDjabrayan et al. demonstrate a direct connection between dNTP metabolism, the cell cycle, and zygotic transcription at the midblastula transition in the Drosophila embryo. Dynamic restriction of dNTP levels is involved in the slowing down of nuclear divisions in the syncytial blastoderm, robust accumulation of zygotic gene products, and morphogenesis. SUMMARYThe thirteen nuclear cleavages that give rise to the Drosophila blastoderm are some of the fastest known cell cycles [1]. Surprisingly, the fertilized egg is provided with at most one-third of the dNTPs needed to complete the thirteen rounds of DNA replication [2]. The rest must be synthesized by the embryo, concurrent with cleavage divisions. What is the reason for the limited supply of DNA building blocks? We propose that frugal control of dNTP synthesis contributes to the well-characterized deceleration of the cleavage cycles and is needed for robust accumulation of zygotic gene products. In support of this model, we demonstrate that when the levels of dNTPs are abnormally high, nuclear cleavages fail to sufficiently decelerate, the levels of zygotic transcription are dramatically reduced, and the embryo catastrophically fails early in gastrulation. Our work reveals a direct connection between metabolism, the cell cycle, and zygotic transcription.

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Section: Resultssupporting

confidence: 76%

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

et al. 2019

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“…However, we find that the rate of production of division proteins, κ p , is proportional (C +D) −1 (Figure S2A-B [20]. However, we note that a linear relationship between cell size and κ(C + D) does not accurately describe all available experimental data [4,7,62] for cell size ( Figure S2C).…”

Section: Discussionmentioning

confidence: 83%

“…The gray line is a linear fit to data from Zheng et al [48]. The red line is an exponential fit to data from Zheng et al [48], Zhu et al [62] and Basan et al [7]. Data from Si et al [4] is shown on y-axis to the right.…”

Section: Proteome Sector Modelmentioning

confidence: 99%

Nutrient-dependent trade-offs between ribosomes and division protein synthesis control bacterial cell size and growth

Serbanescu

Ojkic

Banerjee

2020

Preprint

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Cell size control emerges from a regulated balance between the rates of cell growth and division. In bacteria, simple quantitative laws connect cellular growth rate to ribosome abundance. However, it remains poorly understood how translation regulates bacterial cell size and shapes under growth perturbations. Here we develop a whole-cell model for growth dynamics in rod-shaped bacteria that links ribosomal abundance with cell geometry, division control, and the extracellular environment.Our study reveals that cell shape maintenance under nutrient perturbations requires a balanced trade-off between ribosomes and division protein synthesis. Deviations from this trade-off relationship is predicted under translational perturbations, leading to distinct modes of cell morphological changes, in agreement with single-cell experimental data on Escherichia coli. Furthermore, by calibrating our model with experimental data, we predict how combinations of nutrient-, translational-and shape perturbations can be chosen to optimize bacterial growth fitness and drug resistance.

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“…Their ō were characterized by using run-out protocol followed by Hoechst 33342 staining and microscopic image analysis 3 . e , Comparison between the data in this study and those extracted from Zhu et al 24 . Their ō data were derived from replication origin per genome, and genome equivalents per cell for cells in batch culture.…”

Section: Extended Data Figurementioning

confidence: 92%

“…For fast growth rates where λ is much larger than α / β ≈ 0.28/ h , this is consistent with the wide-spread notion that C + D stays roughly constant for fast growing cells 19 . A number of authors have determined population-averaged C + D or ō at various growth rates for E. coli 3,22–24 ; Michelsen et al 23 in particular obtained data far into the slow-growth regime. When compared to these published data, Eq.…”

mentioning

confidence: 99%

A general quantitative relation linking bacterial cell growth and the cell cycle

Zheng

Bai

Jiang

et al. 2019

Preprint

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The foundation of bacterial cell cycle studies has long resided in two interconnected dogmas between 18 biomass growth, DNA replication, and cell division during exponential growth: the SMK growth law 19 that relates cell mass (a measure of cell size) to growth rate 1 , and Donachie's hypothesis of a growth-20 rate-independent initiation mass 2 . These dogmas have spurred many efforts to understand their 21 molecular bases and physiological consequences 3-12 . Most of these studies focused on fast-growing 22 cells, with doubling times shorter than 60 min. Here, we systematically studied the cell cycle of E. coli 23 for a broad range of doubling times (24 min to over 10 hr), with particular attention on steady-state 24 growth. Surprisingly, we observed that neither dogma held across the range of growth rates examined. 25In their stead, a new linear relation unifying the slow-and fast-growth regimes was revealed between 26 the cell mass and the number of cell divisions it takes to replicate and segregate a newly initiated pair 27 of replication origins. This and other findings in this study suggest a single-cell division model, which 28 not only reproduces the bulk relations observed but also recapitulates the adder phenomenon 29 established recently for stochastically dividing cells 13-15 . These results allowed us to develop 30 quantitative insight into the bacterial cell cycle, providing a firm new foundation for the study of 31 bacterial growth physiology. 32 A fundamental notion in the quantitative study of bacterial physiology is steady state growth 16,17 , where 33the rate of total cell mass growth ( " ) is identical to the rate of cell number growth ( # ). To cover both 34 the slow-and fast-growth regimes, we cultured E. coli K12 MG1655 cells in 32 different growth media 35 with corresponding growth rates ranging from 0.06 to 1.7 h -1 (doubling times ranging from ~700 min to 36 24 min; see Extended Data Table 1). Special care was taken to ensure that all experimental cultures in 37this study lie on the steady-state line " = # , hereafter designated as ; see Extended Data Fig. 1. 38The SMK growth law 1 , long-accepted in the fast-growth regime, states that the population-averaged 39 cellular mass ( ) scales exponentially with growth rate, ~ )* , with a constant parameter ≈ 1 ℎ. 40We examined several measures of , including dry weight, optical density (OD), and cell size (by flow 41 cytometry and microscopic imaging) (Supplementary Methods). For each measure, we found the SMK 42 law to break down for growth rates below 0.7 h -1 ( Fig. 1a-d). Our OD data appear in good agreement 43 with that obtained by Schaechter et al. 1 (green squares in Fig. 1e) for the mostly fast growth rates they 44analyzed, even though they studied a Salmonella strain. We also extracted cell size data from recent 45 studies by Si et al. 3 and Gray et al. 18 , and found their data to be consistent with ours (blue and red symbols, 46 Fig. 1f). Aside from the average cell size, even the size distributions appear to be indistinguishable ...

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Manipulating the Bacterial Cell Cycle and Cell Size by Titrating the Expression of Ribonucleotide Reductase

Cited by 29 publications

References 27 publications

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

Metabolic Regulation of Developmental Cell Cycles and Zygotic Transcription

Nutrient-dependent trade-offs between ribosomes and division protein synthesis control bacterial cell size and growth

A general quantitative relation linking bacterial cell growth and the cell cycle

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