Evidence map›Paper›PMID 32601325›Full record

ArticleScientific reports2020

Mucus layer modeling of human colonoids during infection with enteroaggragative E. coli.

Lixia Liu, Waleska Saitz-Rojas, Rachel Smith, Laura Gonyar, Julie G In, Olga Kovbasnjuk, Nicholas C Zachos, Mark Donowitz, James P Nataro, Fernando Ruiz-Perez

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 59 citations in OpenAlex.

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  14. Nutrition ofEcoSal Plus · 2024
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  18. Review
  19. In Vitro Models for Investigating Intestinal Host-Pathogen Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  20. Sialic acid plays a pivotal role in licensingProceedings of the National Academy of Sciences of the United States of America · 2023
    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

10 authors at 4 institutions in 1 country.

Lixia Liu *Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Waleska Saitz-Rojas *Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Rachel SmithDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Laura GonyarDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Julie G InDepartment of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USA.
Olga KovbasnjukDepartment of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USA.
Nicholas C ZachosDepartment of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mark DonowitzDepartment of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James P NataroDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Fernando Ruiz-PerezDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA. fr3d@virginia.edu.
University of Virginia · USUniversity of New Mexico · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Project 3 - Human colonoids as a model for the pathobiology of EHECP01AI125181 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI KAPER, JAMES B · 2016 to 2025
$18.6M
Human Enteroids as a Model of Host-EHEC InteractionsK01DK106323 · NIDDK · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI IN, JULIE GOEUN · 2016 to 2020
$711k
NIAID NIH HHS P01 AI125181NIDDK NIH HHS K01 DK106323
6 · The paper itself

Abstract

EAEC is a common cause of diarrheal illness worldwide. Pathogenesis is believed to occur in the ileum and colon, where the bacteria adhere and form a robust aggregating biofilm. Among the multiple virulence factors produced by EAEC, the Pic serine protease has been implicated in bacterial colonization by virtue of its mucinolytic activity. Hence, a potential role of Pic in mucus barrier disruption during EAEC infection has been long postulated. In this study, we used human colonoids comprising goblet cells and a thick mucin barrier as an intestinal model to investigate Pic's roles during infection with EAEC. We demonstrated the ability of purified Pic, but not a protease defective Pic mutant to degrade MUC2. Western blot and confocal microscopy analysis revealed degradation of the MUC2 layer in colonoids infected with EAEC, but not with its isogenic EAECpic mutant. Wild-type and MUC2-knockdown colonoids infected with EAEC strains exposed a differential biofilm distribution, greater penetration of the mucus layer and increased colonization of the colonic epithelium by Wild-type EAEC than its isogenic Pic mutant. Higher secretion of pro-inflammatory cytokines was seen in colonoids infected with EAEC than EAECpic. Although commensal E. coli expressing Pic degraded MUC2, it did not show improved mucus layer penetration or colonization of the colonic epithelium. Our study demonstrates a role of Pic in MUC2 barrier disruption in the human intestine and shows that colonoids are a reliable system to study the interaction of pathogens with the mucus layer.

Indexed as

Escherichia coliColonEscherichia coli InfectionsEscherichia coli ProteinsGoblet CellsHumansIntestinal MucosaMucinsSerine EndopeptidasesEscherichia coli ProteinsMucinsPic protein, E coliSerine Endopeptidases

Identifiers

PMID32601325
PMCPMC7324601
OpenAlexW3037480564

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.