Evidence map›Paper›PMID 35881640›Full record

ArticlePLoS neglected tropical diseases2022

The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model.

Emily M Smith, Christen L Grassel, Antonia Papadimas, Jennifer Foulke-Abel, Eileen M Barry

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in PLoS neglected tropical diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
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  7. Current research in food science · 2025
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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

5 authors at 2 institutions in 1 country.

Emily M SmithCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.ORCID 0000-0002-3312-833X
Christen L GrasselCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Antonia PapadimasCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Jennifer Foulke-AbelDepartment of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Eileen M BarryCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
University of Maryland, Baltimore · USJohns Hopkins University · US

Funding

Vaccine strategy for broad spectrum protection agains non-typhoidal salmonellU54AI057168 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI GEDDES, CHRISTOPHER DARREN · 2003 to 2013
$91.5M
Project 3 - Human colonoids as a model for the pathobiology of EHECP01AI125181 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ZACHOS, NICHOLAS CONSTANTINE · 2016 to 2025
$18.6M
Probiotic yeast secreting single-domain antibodies to prevent Clostridium difficile and Campylobacter jejuni diseaseU19AI142725 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 2019 to 2023
$12.5M
Translational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0M
A Human Enteroid Model of Cholera Toxin PathophysiologyK01DK113043 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI FOULKE-ABEL, JENNIFER · 2018 to 2022
$791k
NIAID NIH HHS P01 AI125181NIAID NIH HHS U19 AI142725NIAID NIH HHS U54 AI057168NIDDK NIH HHS K01 DK113043NIDDK NIH HHS P30 DK089502
6 · The paper itself

Abstract

Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens. CFA/I is a major CF that is associated with ETEC that causes moderate-to-severe diarrhea and plays an important role in pathogenesis. The Global Enteric Multicenter Study finding that 78% of CFA/I-expressing ETEC also encode the minor CF CS21 prompted investigation of the combined role of these two CFs. Western blots and electron microscopy demonstrated growth media-dependent and strain-dependent differences in CFA/I and CS21 expression. The critical role of CFA/I in adherence by ETEC strains expressing CFA/I and CS21 was demonstrated using the human enteroid model and a series of CFA/I- and CS21-specific mutants. Furthermore, only anti-CFA/I antibodies inhibited adherence by global ETEC isolates expressing CFA/I and CS21. Delivery of ST and resulting cGMP secretion was measured in supernatants from infected enteroid monolayers, and strain-specific ST delivery and time-dependent cGMP production was observed. Interestingly, cGMP levels were similar across wildtype and CF-deficient strains, reflecting a limitation of this static aerobic infection model. Despite adherence by ETEC and delivery of ST, the enteroid monolayer integrity was not disrupted, as shown by the lack of decrease in transepithelial electrical resistance and the lack of IL-8 cytokines produced during infection. Taken together, these data demonstrate that targeting CFA/I in global clinical CFA/I-CS21 strains is sufficient for adherence inhibition, supporting a vaccine strategy that focuses on blocking major CFs. In addition, the human enteroid model has significant utility for the study of ETEC pathogenesis and evaluation of vaccine-induced functional antibody responses.

Indexed as

Enterotoxigenic Escherichia coliEscherichia coli InfectionsEscherichia coli ProteinsFimbriae ProteinsChildChild, PreschoolDiarrheaEnterotoxinsHumansEnterotoxinsEscherichia coli ProteinsFimbriae Proteins

Identifiers

PMID35881640
PMCPMC9355178
OpenAlexW4288039907

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.