Evidence map›Paper›PMID 30323217›Full record

ArticleNature chemical biology2018

In vivo chloride concentrations surge to proteotoxic levels during acid stress.

Frederick Stull, Hannah Hipp, Randy B Stockbridge, James C A Bardwell

Abstract read
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Donnan potential revealed.Nature communications · 2022
    Article
  7. Article
  8. Stress-Responsive Periplasmic Chaperones in Bacteria.Frontiers in molecular biosciences · 2021
    Review
  9. Review
  10. Phase separation by ssDNA binding protein controlled via protein-protein and protein-DNA interactions.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Protein aggregation in bacteria.FEMS microbiology reviews · 2020
    Review
  12. Article
  13. Compartmentalizing acid stress in bacteria.Nature chemical biology · 2018
    Article
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 at 3 institutions in 1 country.

Frederick StullHoward Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA. fstull@umich.edu.
Hannah HippHoward Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA.
Randy B StockbridgeDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
James C A BardwellHoward Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA. jbardwel@umich.edu.
University of Michigan–Ann Arbor · USHoward Hughes Medical Institute · USMichigan Medicine · US

Funding

Structural and functional analysis of novel microbial membrane proteinsR35GM128768 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Randy B. Stockbridge · 2018 to 2026
$3.7M
Mechanism of an Acid Activated ChaperoneR01GM102829 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARDWELL, JAMES, JAKOB, URSULA H. · 2013 to 2016
$1.8M
Structure, mechanism, and biological role of a microbial fluoride channelR00GM111767 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STOCKBRIDGE, RANDY B. · 2016 to 2018
$737k
Howard Hughes Medical InstituteNIGMS NIH HHS R00 GM111767NIGMS NIH HHS R01 GM102829NIGMS NIH HHS R35 GM128768
6 · The paper itself

Abstract

To successfully colonize the intestine, bacteria must survive passage through the stomach. The permeability of the outer membrane renders the periplasm of Gram-negative bacteria vulnerable to stomach acid, which inactivates proteins. Here we report that the semipermeable nature of the outer membrane allows the development of a strong Donnan equilibrium across this barrier at low pH. As a result, when bacteria are exposed to conditions that mimic gastric juice, periplasmic chloride concentrations rise to levels that exceed 0.6 M. At these chloride concentrations, proteins readily aggregate in vitro. The acid sensitivity of strains lacking acid-protective chaperones is enhanced by chloride, suggesting that these chaperones protect periplasmic proteins both from acidification and from the accompanying accumulation of chloride. These results illustrate how organisms have evolved chaperones to respond to the substantial chemical threat imposed by otherwise innocuous chloride concentrations that are amplified to proteotoxic levels by low-pH-induced Donnan equilibrium effects.

Indexed as

AnionsBacterial Outer Membrane ProteinsCarrier ProteinsChloridesEscherichia coliEscherichia coli ProteinsGastric JuiceGram-Negative BacteriaHumansHydrogen-Ion ConcentrationLipoproteinsMolecular ChaperonesPeriplasmPeriplasmic Binding ProteinsProtein BindingProtein DenaturationAnionsBacterial Outer Membrane ProteinsCarrier ProteinsChloridesdppA protein, E coliEscherichia coli ProteinshdeA protein, E colihdeB protein, E coliLipoproteinsMalE protein, E coliMolecular ChaperonesOppA protein, E coliPeriplasmic Binding ProteinsProteomeSulfates

Identifiers

PMID30323217
PMCPMC6193267
OpenAlexW2897009603

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.