Bacterial cell proliferation: from molecules to cells

Summary In balanced exponential growth, bacteria maintain many properties statistically stable for a long time: cell size, cell cycle time, and more. As these are strongly coupled variables, it is not a-priori obvious which are directly regulated and which are stabilized through interactions. Here, we address this problem by separating timescales in bacterial single-cell dynamics. Disentangling homeostatic set points from fluctuations around them reveals that some variables, such as growth-rate, cell size and cycle time, are “sloppy” with highly volatile set points. Quantifying the relative contribution of environmental and internal sources, we find that sloppiness is primarily driven by the environment. Other variables such as fold-change define “stiff” combinations of coupled variables with robust set points. These results are manifested geometrically as a control manifold in the space of variables: set points span a wide range of values within the manifold, whereas out-of-manifold deviations are constrained. Our work offers a generalizable data-driven approach for identifying control variables in a multidimensional system.

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“…Recent years have seen renewed interest in the classic problem of bacterial growth homeostasis ( Jun et al. 2018 ; Meunier et al. 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Multiple timescales in bacterial growth homeostasis

Stawsky¹,

Vashistha²,

Salman³

et al. 2022

iScience

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“…What triggers the bacterial division? To answer such questions, many studies have deciphered complex intracellular mechanisms, see for instance the recent review [6], while others aim at inferring laws of growth and division out of the observation of population (as in Fig. 1) or lineages (as in Fig.…”

Section: How Does a Cell Divide?mentioning

confidence: 99%

Individual and population approaches for calibrating division rates in population dynamics: Application to the bacterial cell cycle

Doumic,

Hoffmann

2021

Preprint

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Modelling, analysing and inferring triggering mechanisms in population reproduction is fundamental in many biological applications. It is also an active and growing research domain in mathematical biology. In this chapter, we review the main results developed over the last decade for the estimation of the division rate in growing and dividing populations in a steady environment. These methods combine tools borrowed from PDE's and stochastic processes, with a certain view that emerges from mathematical statistics. A focus on the application to the bacterial cell division cycle provides a concrete presentation, and may help the reader to identify major new challenges in the field.

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“…Bacterial proliferation has been extensively studied for the past decades in a few model species (e.g., Escherichia coli, Caulobacter crescentus and Bacillus subtilis ), revealing not only specific strategies but also general principles that govern streamlined cell cycle progression. For instance, these bacteria use exquisite mechanisms to tightly coordinate key cellular processes in space and time, such as cell growth, DNA replication, chromosome segregation, and cell division [1,2]. Examining how external cues impact the proliferation of those species further allowed to identify dependencies between fluctuating nutrients, cell size, and growth rate, which define the bacterial growth law [3–7].…”

Section: Introductionmentioning

confidence: 99%

Modulation of prey size reveals adaptability and robustness in the cell cycle of an intracellular predator

Santin

Lamot

Kaljević

et al. 2022

Preprint

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Despite the remarkable diversity of bacterial lifestyles, the sophisticated regulatory networks underlying bacterial replication have only been investigated in a limited number of model species so far. In bacteria that do not rely on canonical binary division for proliferation, the coordination of major cellular processes is still mysterious. Moreover, bacterial growth and division remain largely unexplored within spatially confined niches where nutrients are limited. This includes the lifecycle of the model endobiotic predatory bacterium Bdellovibrio bacteriovorus, which grows by filamentation within its host or prey cells and produces a variable number of daughter cells. Here, we examined how the size of the micro-compartment in which predators replicate (i.e., the prey bacterium) impacts their cell cycle progression at the single-cell level. Using Escherichia coli with genetically encoded size differences, we show that the duration of the predator cell cycle scales with prey size. As a result, the size of the prey determines the number of predator offspring, through a relationship that is maintained across prey species. Strikingly, the nutritional quality of the prey cell determined the specific growth rate of predators regardless of prey size, reminiscent of the effect of medium composition on the growth of other bacteria. Tuning the predatory cell cycle by modulating prey dimensions also allowed us to reveal invariable temporal connections between key cellular processes. Altogether, our data uncover adaptability and robustness shaping the enclosed replication of B. bacteriovorus. Consequently, predators optimally exploit the finite prey resources and space while ensuring a strict cell cycle progression. This study opens the way to explore diverse cell cycle control strategies by extending their characterization to intracellular lifestyles, beyond canonical models and growth conditions.

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Bacterial cell proliferation: from molecules to cells

Cited by 25 publications

References 227 publications

Multiple timescales in bacterial growth homeostasis

Multiple timescales in bacterial growth homeostasis

Individual and population approaches for calibrating division rates in population dynamics: Application to the bacterial cell cycle

Modulation of prey size reveals adaptability and robustness in the cell cycle of an intracellular predator

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