Evidence map›Paper›PMID 39138228›Full record

ArticleNature communications2024

A pH-sensitive motif in an outer membrane protein activates bacterial membrane vesicle production.

Ruchika Dehinwal, Tata Gopinath, Richard D Smith, Robert K Ernst, Dieter M Schifferli, Matthew K Waldor, Francesca M Marassi

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
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  11. In situ NMR reveals a pH sensor motif in an outer membrane protein that drives bacterial vesicle production.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. 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

7 authors.

Ruchika DehinwalDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, USA.ORCID 0000-0002-7085-4760
Tata GopinathDepartment of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
Richard D SmithDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA.
Robert K ErnstDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA.ORCID 0000-0001-5016-8694
Dieter M SchifferliDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. dmschiff@vet.upenn.edu.ORCID 0000-0002-5540-2969
Matthew K WaldorDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, USA. mwaldor@bwh.harvard.edu.ORCID 0000-0003-1843-7000
Francesca M MarassiDepartment of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. fmarassi@mcw.edu.ORCID 0000-0003-2695-5844

Funding

Membrane Protein Effectors of Pathogen Interactions With HostR35GM118186 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Francesca M Marassi · 2016 to 2026
$8.5M
Vibrio cholerae intestinal colonization and vaccine developmentR01AI042347 · NIAID · TUFTS UNIVERSITY BOSTON · PI WALDOR, MATTHEW K · 1998 to 2025
$7.3M
Molecular Biology and Virulence of CTX PhageR37AI042347 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI WALDOR, MATTHEW K · 2008 to 2017
$3.8M
MS Diagnostic Bacterial Identification LibraryR01AI147314 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ERNST, ROBERT K, GOODLETT, DAVID ROBINSON · 2020 to 2024
$2.3M
Outer Membrane Vesicle (OMV) Production by Salmonella PhoPQ and Inflammasome ActivationR21AI139982 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SCHIFFERLI, DIETER M. · 2019 to 2020
$443k
Howard Hughes Medical Institute (HHMI) CC30430NIAID NIH HHS R01 AI042347NIAID NIH HHS R01 AI147314NIAID NIH HHS R21 AI139982NIAID NIH HHS R37 AI042347NIGMS NIH HHS R35 GM118186
6 · The paper itself

Abstract

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria have key roles in cell envelope homeostasis, secretion, interbacterial communication, and pathogenesis. The facultative intracellular pathogen Salmonella Typhimurium increases OMV production inside the acidic vacuoles of host cells by changing expression of its outer membrane proteins and modifying the composition of lipid A. However, the molecular mechanisms that translate pH changes into OMV production are not completely understood. Here, we show that the outer membrane protein PagC promotes OMV production through pH-dependent interactions between its extracellular loops and surrounding lipopolysaccharide (LPS). Structural comparisons and mutational studies indicate that a pH-responsive amino acid motif in PagC extracellular loops, containing PagC-specific histidine residues, is crucial for OMV formation. Molecular dynamics simulations suggest that protonation of histidine residues leads to changes in the structure and flexibility of PagC extracellular loops and their interactions with the surrounding LPS, altering membrane curvature. Consistent with that hypothesis, mimicking acidic pH by mutating those histidine residues to lysine increases OMV production. Thus, our findings reveal a mechanism for sensing and responding to environmental pH and for control of membrane dynamics by outer membrane proteins.

Indexed as

Bacterial Outer Membrane ProteinsLipopolysaccharidesMolecular Dynamics SimulationSalmonella typhimuriumAmino Acid MotifsBacterial Outer MembraneHistidineHydrogen-Ion ConcentrationBacterial Outer Membrane ProteinsHistidineLipopolysaccharides

Identifiers

PMID39138228
PMCPMC11322160

What OpenQuestion holds

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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.