ppGpp is a bacterial cell size regulator

Ferhat Büke, Jacopo Grilli, Marco Cosentino Lagomarsino, Gregory Bokinsky, Sander J. Tans*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)
7 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)870-877.e5
JournalCurrent Biology
Issue number4
Publication statusPublished - 2022

Bibliographical note

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care
Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.


  • adder mechanism
  • cell size
  • cell size homeostasis
  • Escherichia coli
  • growth rate
  • lineage tree analysis
  • microfluidics
  • microscopy
  • ppGpp
  • single cell analysis


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