Evidence map›Paper›PMID 25330071›Full record

ArticlePLoS pathogens2014

The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration.

Jennifer A Gaddy, Jana N Radin, John T Loh, M Blanca Piazuelo, Thomas E Kehl-Fie, Alberto G Delgado, Florin T Ilca, Richard M Peek, Timothy L Cover, Walter J Chazin and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
9.4field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 87 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. The Effects of Vitamins and Micronutrients onJournal of immunology research · 2022
    Review
  14. Yersiniabactin contributes to overcoming zinc restriction duringProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. The impact of metal availability on immune function during infection.Trends in endocrinology and metabolism: TEM · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 1 country.

Jennifer A GaddyVeterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Jana N RadinDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
John T LohDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
M Blanca PiazueloDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Thomas E Kehl-FieDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Alberto G DelgadoDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Florin T IlcaDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Richard M PeekDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Timothy L CoverVeterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Walter J ChazinDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Center for Structural Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Eric P SkaarVeterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee, United States of America; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Holly M Scott AlgoodVeterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Vanderbilt University · USVA Tennessee Valley Healthcare System · US

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Role of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 2009 to 2026
$27.5M
Project 3 - Molecular Signatures of Gastric Carcinogenesis in the Host Response to H. pyloriP01CA028842 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1985 to 2019
$15.8M
H.Pylori Relationship to Digestive Diseases and CancerR01CA077955 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2003 to 2026
$9.7M
Structure-function analysis of H. pylori VacAR01AI039657 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI TIMOTHY L COVER · 1996 to 2026
$8.3M
Host-mediated zinc sequestration during Acinetobacter baumannii infectionR01AI101171 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WALTER J. CHAZIN, DAVID P. GIEDROC · 2013 to 2026
$8.2M
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Helicobacter Pylori and Gastrointestinal BiologyR01DK058587 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PEEK, RICHARD M. · 2001 to 2024
$7.8M
Analysis of the H. Pylori cag pathogenicity islandR01AI068009 · NIAID · VANDERBILT UNIVERSITY · PI COVER, TIMOTHY L · 2008 to 2012
$1.9M
H PYLORI RELATIONSHIP TO DIGESTIVE DISEASES AND CANCERR29CA077955 · NCI · VANDERBILT UNIVERSITY · PI PEEK, RICHARD M · 1997 to 2001
$294k
Adaptation of Staphylococcus aureus to Mn and Zn starvation imposed by the hostK22AI104805 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KEHL-FIE, THOMAS EVERETT · 2014 to 2015
$264k
The role of Th17 cytokines in H.pylori infectionI01BX000915 · VA · VETERANS HEALTH ADMINISTRATION · PI HOLLY Marie Scott ALGOOD · 2011 to 2026
–
BLRD VA I01 BX000627BLRD VA I01 BX000915BLRD VA IK2 BX001701NCI NIH HHS CA 77955NCI NIH HHS P01 CA028842NCI NIH HHS P01 CA116087NCI NIH HHS R01 CA077955NCI NIH HHS R29 CA077955NIAID NIH HHS K22 AI104805NIAID NIH HHS K22 AI104805-01NIAID NIH HHS R01 AI039657NIAID NIH HHS R01 AI068009NIAID NIH HHS R01 AI101171NIDDK NIH HHS DK 58587NIDDK NIH HHS P30 DK058404NIDDK NIH HHS P30DK058404NIDDK NIH HHS R01 DK058587NIGMS NIH HHS T32 GM008320
6 · The paper itself

Abstract

Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters essential nutrient metals away from invading pathogenic bacteria. Neutrophils participate in this process by producing several metal chelating proteins, including lactoferrin and calprotectin (CP). As neutrophils are an important component of the inflammatory response directed against the bacterium Helicobacter pylori, a major risk factor for gastric cancer, it was hypothesized that CP plays a role in the host response to H. pylori. Utilizing a murine model of H. pylori infection and gastric epithelial cell co-cultures, the role CP plays in modifying H. pylori -host interactions and the function of the cag Type IV Secretion System (cag T4SS) was investigated. This study indicates elevated gastric levels of CP are associated with the infiltration of neutrophils to the H. pylori-infected tissue. When infected with an H. pylori strain harboring a functional cag T4SS, calprotectin-deficient mice exhibited decreased bacterial burdens and a trend toward increased cag T4SS -dependent inflammation compared to wild-type mice. In vitro data demonstrate that culturing H. pylori with sub-inhibitory doses of CP reduces the activity of the cag T4SS and the biogenesis of cag T4SS-associated pili in a zinc-dependent fashion. Taken together, these data indicate that zinc homeostasis plays a role in regulating the proinflammatory activity of the cag T4SS.

Indexed as

Helicobacter pyloriAnimalsBacterial ProteinsCoculture TechniquesDisease Models, AnimalEpithelial CellsGastric MucosaHelicobacter InfectionsHomeostasisLeukocyte L1 Antigen ComplexMiceRisk FactorsStomach NeoplasmsZincBacterial ProteinsLeukocyte L1 Antigen ComplexZinc

Identifiers

PMID25330071
PMCPMC4199781
OpenAlexW1992196644

What OpenQuestion holds

Textmetadata
LicenceCC0
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.