TY - JOUR
T1 - ppGpp is a bacterial cell size regulator
AU - Büke, Ferhat
AU - Grilli, Jacopo
AU - Cosentino Lagomarsino, Marco
AU - Bokinsky, Gregory
AU - Tans, Sander J.
PY - 2022
Y1 - 2022
N2 - Growth and division are central to cell size. Bacteria achieve size homeostasis by dividing when growth has added a constant size since birth, termed the adder principle, by unknown mechanisms.1,2 Growth is well known to be regulated by guanosine tetraphosphate (ppGpp), which controls diverse processes from ribosome production to metabolic enzyme activity and replication initiation and whose absence or excess can induce stress, filamentation, and small growth-arrested cells.3–6 These observations raise unresolved questions about the relation between ppGpp and size homeostasis mechanisms during normal exponential growth. Here, to untangle effects of ppGpp and nutrients, we gained control of cellular ppGpp by inducing the synthesis and hydrolysis enzymes RelA and Mesh1. We found that ppGpp not only exerts control over the growth rate but also over cell division and thus the steady state cell size. In response to changes in ppGpp level, the added size already establishes its new constant value while the growth rate still adjusts, aided by accelerated or delayed divisions. Moreover, the magnitude of the added size and resulting steady-state birth size correlate consistently with the ppGpp level, rather than with the growth rate, which results in cells of different size that grow equally fast. Our findings suggest that ppGpp serves as a key regulator that coordinates cell size and growth control.
AB - Growth and division are central to cell size. Bacteria achieve size homeostasis by dividing when growth has added a constant size since birth, termed the adder principle, by unknown mechanisms.1,2 Growth is well known to be regulated by guanosine tetraphosphate (ppGpp), which controls diverse processes from ribosome production to metabolic enzyme activity and replication initiation and whose absence or excess can induce stress, filamentation, and small growth-arrested cells.3–6 These observations raise unresolved questions about the relation between ppGpp and size homeostasis mechanisms during normal exponential growth. Here, to untangle effects of ppGpp and nutrients, we gained control of cellular ppGpp by inducing the synthesis and hydrolysis enzymes RelA and Mesh1. We found that ppGpp not only exerts control over the growth rate but also over cell division and thus the steady state cell size. In response to changes in ppGpp level, the added size already establishes its new constant value while the growth rate still adjusts, aided by accelerated or delayed divisions. Moreover, the magnitude of the added size and resulting steady-state birth size correlate consistently with the ppGpp level, rather than with the growth rate, which results in cells of different size that grow equally fast. Our findings suggest that ppGpp serves as a key regulator that coordinates cell size and growth control.
KW - adder mechanism
KW - cell size
KW - cell size homeostasis
KW - Escherichia coli
KW - growth rate
KW - lineage tree analysis
KW - microfluidics
KW - microscopy
KW - ppGpp
KW - single cell analysis
UR - http://www.scopus.com/inward/record.url?scp=85125207137&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2021.12.033
DO - 10.1016/j.cub.2021.12.033
M3 - Article
AN - SCOPUS:85125207137
VL - 32
SP - 870-877.e5
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 4
ER -