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Fundamental limits on the rate of bacterial growth and their influence on proteomic composition

Belliveau, Nathan M. and Chure, Griffin and Hueschen, Christina L. and Garcia, Hernan G. and Kondev, Jane and Fisher, Daniel S. and Theriot, Julie A. and Phillips, Rob (2021) Fundamental limits on the rate of bacterial growth and their influence on proteomic composition. Cell Systems, 12 (9). pp. 924-944. ISSN 2405-4712. PMCID PMC8460600. doi:10.1016/j.cels.2021.06.002.

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Despite abundant measurements of bacterial growth rate, cell size, and protein content, we lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we estimate the basic requirements and physical constraints on steady-state growth by considering key processes in cellular physiology across a collection of Escherichia coli proteomic data covering ≈4,000 proteins and 36 growth rates. Our analysis suggests that cells are predominantly tuned for the task of cell doubling across a continuum of growth rates; specific processes do not limit growth rate or dictate cell size. We present a model of proteomic regulation as a function of nutrient supply that reconciles observed interdependences between protein synthesis, cell size, and growth rate and propose that a theoretical inability to parallelize ribosomal synthesis places a firm limit on the achievable growth rate. A record of this paper’s transparent peer review process is included in the supplemental information.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper ItemData/Code ItemData
Belliveau, Nathan M.0000-0002-1536-1963
Chure, Griffin0000-0002-2216-2057
Hueschen, Christina L.0000-0002-3437-2895
Kondev, Jane0000-0001-7522-7144
Theriot, Julie A.0000-0002-2334-2535
Phillips, Rob0000-0003-3082-2809
Alternate Title:Fundamental limits on the rate of bacterial growth
Additional Information:© 2021 Elsevier Inc. Received 10 December 2020, Revised 12 April 2021, Accepted 4 June 2021, Available online 1 July 2021. We thank Matthias Heinemann, Alexander Schmidt, and Gene-Wei Li for additional input regarding their data. We also thank all members of the Phillips, Theriot, Kondev, Garcia labs, as well as Ron Milo and Terry Hwa for useful discussions. We thank Suzannah M. Beeler, Jonas Cremer, Avi Flamholz, Soichi Hirokawa, and Manuel Razo-Mejia for reading and providing comments on drafts of this manuscript. R.P. is supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the NIH 1R35 GM118043 (MIRA). J.A.T. is supported by the Howard Hughes Medical Institute, and NIH grant R37-AI036929. N.M.B is a HHMI fellow of the Jane Coffin Childs Memorial Fund. H.G.G. is supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface, the Sloan Research Foundation, the Human Frontiers Science Program, the Searle Scholars Program, the Shurl & Kay Curci Foundation, the Hellman Foundation, the NIH Director’s New Innovator Award (DP2 OD024541-01), and an NSF CAREER award (1652236). D.S.F. is supported by an NSF award (PHY-1607606) and the NIH (NIH R01-AI13699201). Author contributions: N.M.B., G.C., C.L.H., H.G.G., J.K., D.S.F., J.A.T., and R.P. conceived the project. N.M.B. and G.C. collected and analyzed data from the literature. G.C., N.M.B., and R.P. performed the order-of-magnitude estimates. R.P., J.A.T., J.K., H.G.G., and D.S.F. supervised the theoretical analyses. N.M.B., G.C., R.P., J.A.T., and C.L.H. wrote and edited the manuscript. J.A.T. is chief scientific advisor at the Allen Institute for Cell Science (Seattle, WA, 98109). The authors otherwise declare no competing interests.
Group:Rosen Bioengineering Center
Funding AgencyGrant Number
La Fondation Pierre Gilles de GennesUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIH1R35 GM118043
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Hellman FoundationUNSPECIFIED
NIHDP2 OD024541-01
Subject Keywords:microbial physiology; proteomics; cellular growth; bacteria; cell size; order-of-magnitude estimation; physical biology; microbial growth laws
Issue or Number:9
PubMed Central ID:PMC8460600
Record Number:CaltechAUTHORS:20201021-080615473
Persistent URL:
Official Citation:Nathan M. Belliveau, Griffin Chure, Christina L. Hueschen, Hernan G. Garcia, Jane Kondev, Daniel S. Fisher, Julie A. Theriot, Rob Phillips, Fundamental limits on the rate of bacterial growth and their influence on proteomic composition, Cell Systems, Volume 12, Issue 9, 2021, Pages 924-944.e2, ISSN 2405-4712,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106178
Deposited By: Tony Diaz
Deposited On:21 Oct 2020 16:46
Last Modified:28 Sep 2021 17:51

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