Evidence map›Paper›PMID 31819215›Full record

ArticleNature microbiology2020

Regulation underlying hierarchical and simultaneous utilization of carbon substrates by flux sensors in Escherichia coli.

Hiroyuki Okano, Rutger Hermsen, Karl Kochanowski, Terence Hwa

Abstract read
In one paragraph

Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed.

  1. Sodium ion stress accelerates cell lysis inApplied and environmental microbiology · 2026
    Article
  2. A systems-level atlas of carbon-response transcriptional states inProceedings of the National Academy of Sciences of the United States of America · 2026
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  13. Cytoplasmic MgProceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Hiroyuki Okano *Department of Physics, University of California at San Diego, La Jolla, CA, USA. okanoh@physics.ucsd.edu.ORCID http://orcid.org/0000-0001-8198-1354
Rutger Hermsen *Theoretical Biology Group, Department of Biology, Faculty of Science, Utrecht University, Utrecht, the Netherlands. r.hermsen@uu.nl.ORCID http://orcid.org/0000-0003-4633-4877
Karl KochanowskiInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-1884-7694
Terence HwaDepartment of Physics, University of California at San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-1837-6842

Funding

Quantitative Studies of Bacterial Growth PhysiologyR01GM095903 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HWA, TERENCE · 2011 to 2023
$3.8M
Quantitative Studies of Metabolic Switches in enteric bacteriaR01GM109069 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HWA, TERENCE · 2014 to 2022
$3.0M
NIGMS NIH HHS R01 GM095903NIGMS NIH HHS R01 GM109069
6 · The paper itself

Abstract

Many microorganisms exhibit nutrient preferences, exemplified by the 'hierarchical' consumption of certain carbon substrates. Here, we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates. A detailed study of glycerol uptake finds that it is fully suppressed if the uptake flux of another glycolytic substrate exceeds a threshold, which is set to the influx obtained when grown on glycerol alone. Below this threshold, limited glycerol uptake is 'supplemented' such that the total carbon uptake is maintained at the threshold. This behaviour results from total-flux feedback mediated by cAMP-Crp signalling but also requires inhibition by the regulator fructose 1,6-bisphosphate, which senses the upper-glycolytic flux and ensures that glycerol uptake defers to other glycolytic substrates but not to gluconeogenic ones. A quantitative model reproduces all of the observed utilization patterns, including those of key mutants. The proposed mechanism relies on the differential regulation of uptake enzymes and requires a specific operon organization. This organization is found to be conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microorganisms.

Indexed as

Gene Expression Regulation, BacterialCarbonCatabolite RepressionCyclic AMPCyclic AMP Receptor ProteinEscherichia coliEscherichia coli ProteinsFeedback, PhysiologicalGlycerolGlycolysisModels, BiologicalRepressor ProteinsSignal TransductionCarboncrp protein, E coliCyclic AMPCyclic AMP Receptor ProteinEscherichia coli ProteinsGlpR protein, E coliGlycerolRepressor Proteins

Identifiers

PMID31819215
PMCPMC6925339

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.