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

2019 ◽  
Author(s):  
Hai Zheng ◽  
Yang Bai ◽  
Meiling Jiang ◽  
Taku A. Tokuyasu ◽  
Xiongliang Huang ◽  
...  

The foundation of bacterial cell cycle studies has long resided in two interconnected dogmas between biomass growth, DNA replication, and cell division during exponential growth: the SMK growth law that relates cell mass (a measure of cell size) to growth rate1, and Donachie’s hypothesis of a growth-rate-independent initiation mass2. These dogmas have spurred many efforts to understand their molecular bases and physiological consequences3–12. Most of these studies focused on fast-growing cells, with doubling times shorter than 60 min. Here, we systematically studied the cell cycle of E. coli for a broad range of doubling times (24 min to over 10 hr), with particular attention on steady-state growth. Surprisingly, we observed that neither dogma held across the range of growth rates examined. In their stead, a new linear relation unifying the slow- and fast-growth regimes was revealed between the cell mass and the number of cell divisions it takes to replicate and segregate a newly initiated pair of replication origins. This and other findings in this study suggest a single-cell division model, which not only reproduces the bulk relations observed but also recapitulates the adder phenomenon established recently for stochastically dividing cells13–15. These results allowed us to develop quantitative insight into the bacterial cell cycle, providing a firm new foundation for the study of bacterial growth physiology.

Development ◽  
1987 ◽  
Vol 100 (1) ◽  
pp. 125-134 ◽  
Author(s):  
C.L. Garbutt ◽  
J.C. Chisholm ◽  
M.H. Johnson

The influence of cell division order on the establishment of the embryonic-abembryonic axis (EA axis) of the mouse embryo was investigated. Aggregate embryos were constructed in which a labelled cell (or pair of cells) was combined with a group of unlabelled cells all of which were up to one cell cycle earlier or later in their progress through development to the blastocyst stage. The aggregates were cultured first to the nascent blastocyst stage and then to the expanded blastocyst stage. The positions of the progeny of the labelled cells in relation to the nascent blastocoel and to the orientation of the embryonic-abembryonic axis were recorded. It was concluded that cell division order does influence the establishment of the EA axis, early dividing cells tending to be associated with the nascent blastocoel and the site of the nascent blastocoel tending to mark the site of the abembryonic pole. However, the influence of division order was diminished by a requirement for intercellular cooperation during blastocoel formation and by a counteracting influence of division order arising from its effects on the allocation of cells to the inner cell mass.


2020 ◽  
Author(s):  
Kristen Schroeder ◽  
Kristina Heinrich ◽  
Ines Neuwirth ◽  
Kristina Jonas

AbstractThe highly conserved chaperonin GroESL performs a crucial role in protein folding, however the essential cellular pathways that rely on this chaperone are underexplored. Loss of GroESL leads to severe septation defects in diverse bacteria, suggesting the folding function of GroESL may be integrated with the bacterial cell cycle at the point of cell division. Here, we describe new connections between GroESL and the bacterial cell cycle, using the model organism Caulobacter crescentus. Using a proteomics approach, we identify candidate GroESL client proteins that become insoluble or are degraded specifically when GroESL folding is insufficient, revealing several essential proteins that participate in cell division and peptidoglycan biosynthesis. We demonstrate that other cell cycle events such as DNA replication and chromosome segregation are able to continue when GroESL folding is insufficient, and find that deficiency of the bacterial actin homologue FtsA function mediates the GroESL-dependent block in cell division. Our data suggest that a GroESL-FtsA interaction is required to maintain normal dynamics of the FtsZ scaffold and divisome functionality in C. crescentus. In addition to supporting FtsA function, we show that GroESL is required to maintain the flow of peptidoglycan precursors into the growing cell wall. Linking a chaperone to cell division may be a conserved way to coordinate environmental and internal cues that signal when it is safe to divide.ImportanceAll organisms depend on mechanisms that protect proteins from misfolding and aggregation. GroESL is a highly conserved molecular chaperone that functions to prevent protein aggregation in organisms ranging from bacteria to humans. Despite detailed biochemical understanding of GroESL function, the in vivo pathways that strictly depend on this chaperone remain poorly defined in most species. This study provides new insights into how GroESL is linked to the bacterial cell division machinery, a crucial target of current and future antimicrobial agents. We identify a functional interaction between GroESL and FtsA, a conserved bacterial actin homologue, suggesting that as in eukaryotes, some bacteria exhibit a connection between cytoskeletal actin proteins and chaperonins. Our work further defines how GroESL is integrated with cell wall synthesis, and illustrates how highly conserved folding machines ensure the functioning of fundamental cellular processes during stress.


mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Kristen Schroeder ◽  
Kristina Heinrich ◽  
Ines Neuwirth ◽  
Kristina Jonas

ABSTRACT The highly conserved chaperonin GroESL performs a crucial role in protein folding; however, the essential cellular pathways that rely on this chaperone are underexplored. Loss of GroESL leads to severe septation defects in diverse bacteria, suggesting the folding function of GroESL may be integrated with the bacterial cell cycle at the point of cell division. Here, we describe new connections between GroESL and the bacterial cell cycle using the model organism Caulobacter crescentus. Using a proteomics approach, we identify candidate GroESL client proteins that become insoluble or are degraded specifically when GroESL folding is insufficient, revealing several essential proteins that participate in cell division and peptidoglycan biosynthesis. We demonstrate that other cell cycle events, such as DNA replication and chromosome segregation, are able to continue when GroESL folding is insufficient. We further find that deficiency of two FtsZ-interacting proteins, the bacterial actin homologue FtsA and the constriction regulator FzlA, mediate the GroESL-dependent block in cell division. Our data show that sufficient GroESL is required to maintain normal dynamics of the FtsZ scaffold and divisome functionality in C. crescentus. In addition to supporting divisome function, we show that GroESL is required to maintain the flow of peptidoglycan precursors into the growing cell wall. Linking a chaperone to cell division may be a conserved way to coordinate environmental and internal cues that signal when it is safe to divide. IMPORTANCE All organisms depend on mechanisms that protect proteins from misfolding and aggregation. GroESL is a highly conserved molecular chaperone that functions to prevent protein aggregation in organisms ranging from bacteria to humans. Despite detailed biochemical understanding of GroESL function, the in vivo pathways that strictly depend on this chaperone remain poorly defined in most species. This study provides new insights into how GroESL is linked to the bacterial cell division machinery, a crucial target of current and future antimicrobial agents. We identify a functional interaction between GroESL and the cell division proteins FzlA and FtsA, which modulate Z-ring function. FtsA is a conserved bacterial actin homologue, suggesting that as in eukaryotes, some bacteria exhibit a connection between cytoskeletal actin proteins and chaperonins. Our work further defines how GroESL is integrated with cell wall synthesis and illustrates how highly conserved folding machines ensure the functioning of fundamental cellular processes during stress.


2021 ◽  
Vol 12 ◽  
Author(s):  
Anne Galinier ◽  
Elodie Foulquier ◽  
Frédérique Pompeo

To survive and adapt to changing nutritional conditions, bacteria must rapidly modulate cell cycle processes, such as doubling time or cell size. Recent data have revealed that cellular metabolism is a central regulator of bacterial cell cycle. Indeed, proteins that can sense precursors or metabolites or enzymes, in addition to their enzymatic activities involved in metabolism, were shown to directly control cell cycle processes in response to changes in nutrient levels. Here we focus on cell elongation and cell division in the Gram-positive rod-shaped bacterium Bacillus subtilis and we report evidences linking these two cellular processes to environmental nutritional availability and thus metabolic cellular status.


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