Evidence map›Paper›PMID 37714857›Full record

ArticleNature communications2023

Mechanism of outer membrane destabilization by global reduction of protein content.

Irina V Mikheyeva, Jiawei Sun, Kerwyn Casey Huang, Thomas J Silhavy

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
11.6field-weighted citation impact, top 1% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. A mechanism for substrate quality control in outer membrane protein assembly.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
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  17. Immobile lipopolysaccharides and outer membrane proteins differentially segregate in growingProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
  19. Review
  20. Sustainable, scalable nanotechnology approach using filtrate fromFrontiers in cellular and infection microbiology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Irina V Mikheyeva *Department of Molecular Biology, Princeton University, Princeton, NJ, 08540, USA.ORCID http://orcid.org/0000-0001-7584-9947
Jiawei Sun *Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Kerwyn Casey HuangDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA. kchuang@stanford.edu.ORCID http://orcid.org/0000-0002-8043-8138
Thomas J SilhavyDepartment of Molecular Biology, Princeton University, Princeton, NJ, 08540, USA. tsilhavy@princeton.edu.ORCID http://orcid.org/0000-0001-7672-5153
Princeton University · USChan Zuckerberg Initiative (United States) · USStanford University · US

Funding

Biogenesis and maintenance of the outer membrane of Gram-negative bacteriaR35GM118024 · NIGMS · PRINCETON UNIVERSITY · PI SILHAVY, THOMAS J. · 2016 to 2025
$8.1M
Molecular mechanisms of Gram-negative outer membrane organizationF32GM139232 · NIGMS · PRINCETON UNIVERSITY · PI MIKHEYEVA-BRIDGES, IRINA V. · 2020 to 2022
$119k
NIGMS NIH HHS F32 GM139232NIGMS NIH HHS R35 GM118024
6 · The paper itself

Abstract

The outer membrane (OM) of Gram-negative bacteria such as Escherichia coli is an asymmetric bilayer with the glycolipid lipopolysaccharide (LPS) in the outer leaflet and glycerophospholipids in the inner. Nearly all integral OM proteins (OMPs) have a characteristic β-barrel fold and are assembled in the OM by the BAM complex, which contains one essential β-barrel protein (BamA), one essential lipoprotein (BamD), and three non-essential lipoproteins (BamBCE). A gain-of-function mutation in bamA enables survival in the absence of BamD, showing that the essential function of this protein is regulatory. Here, we demonstrate that the global reduction in OMPs caused by BamD loss weakens the OM, altering cell shape and causing OM rupture in spent medium. To fill the void created by OMP loss, phospholipids (PLs) flip into the outer leaflet. Under these conditions, mechanisms that remove PLs from the outer leaflet create tension between the OM leaflets, which contributes to membrane rupture. Rupture is prevented by suppressor mutations that release the tension by halting PL removal from the outer leaflet. However, these suppressors do not restore OM stiffness or normal cell shape, revealing a possible connection between OM stiffness and cell shape.

Indexed as

Escherichia coli ProteinsMembrane ProteinsBacterial Outer Membrane ProteinsCell ShapeEscherichia coliGain of Function MutationGlycerophospholipidsBacterial Outer Membrane ProteinsBamA protein, E coliEscherichia coli ProteinsGlycerophospholipidsMembrane Proteins

Identifiers

PMID37714857
PMCPMC10504340
OpenAlexW4386774837

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.