Evidence map›Paper›PMID 31756188›Full record

ArticlePLoS neglected tropical diseases2019

Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli.

F Matthew Kuhlmann, John Martin, Tracy H Hazen, Tim J Vickers, Madeline Pashos, Pablo C Okhuysen, Oscar G Gómez-Duarte, Elizabeth Cebelinski, Dave Boxrud, Felipe Del Canto and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

34 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Complete genomes ofMicrobiology resource announcements · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Recent progress in enterotoxigenicInfection and immunity · 2025
    Review
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  9. Review
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  13. Production of a new tetravalent vaccine targeting fimbriae and enterotoxin of enterotoxigenicCanadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2024
    Article
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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

15 authors at 8 institutions in 3 countries.

F Matthew KuhlmannDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0003-1085-0589
John MartinDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Tracy H HazenDepartment of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Tim J VickersDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Madeline PashosDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-0020-3030
Pablo C OkhuysenThe Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Oscar G Gómez-DuarteDepartment of Pediatrics, Division of Infectious Diseases, University at Buffalo, The State University of New York, Buffalo, New York, United States of America.
Elizabeth CebelinskiMinnesota Department of Health, St. Paul, Minnesota, United States of America.
Dave BoxrudMinnesota Department of Health, St. Paul, Minnesota, United States of America.
Felipe Del CantoPrograma de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Roberto VidalPrograma de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Firdausi QadriInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Makedonka MitrevaDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-9572-3436
David A RaskoDepartment of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.ORCID 0000-0002-7337-7154
James M FleckensteinDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-1148-697X
Washington University in St. Louis · USJames S. McDonnell Foundation · USMinnesota Department of Health · USUniversity of Chile · CLUniversity of Maryland, Baltimore · USInternational Centre for Diarrhoeal Disease Research · BDThe University of Texas MD Anderson Cancer Center · USUniversity at Buffalo, State University of New York · US

Funding

Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Technology CoreU19AI110820 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI RASKO, DAVID A · 2014 to 2023
$36.5M
Novel Antigen Identification for an Enterotoxigenic E. coli VaccineR01AI089894 · NIAID · WASHINGTON UNIVERSITY · PI Zachary T. Berndsen, James Michael Fleckenstein · 2010 to 2026
$7.4M
Studies on Emergent Diarrheagenic E. coli PathogensR01AI095346 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GOMEZ, OSCAR G · 2013 to 2017
$1.9M
Molecular Microbiology of Enterotoxigenic E. coli Pathogen-Host InteractionsR01AI126887 · NIAID · WASHINGTON UNIVERSITY · PI FLECKENSTEIN, JAMES MICHAEL · 2016 to 2020
$1.6M
Gene Polymorphisms Predisposing to Infectious DiarrheaR01AI054948 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI OKHUYSEN, PABLO C · 2003 to 2007
$1.6M
Accelerating Translational Development of Novel Antigens for an Enterotoxigenic E. coli VaccineK23AI130389 · NIAID · WASHINGTON UNIVERSITY · PI KUHLMANN, FREDERICK M · 2017 to 2021
$807k
BLRD VA I01 BX001469BLRD VA I01 BX004825NCATS NIH HHS UL1 TR000448NIAID NIH HHS K23 AI130389NIAID NIH HHS R01 AI054948NIAID NIH HHS R01 AI089894NIAID NIH HHS R01 AI095346NIAID NIH HHS R01 AI126887NIAID NIH HHS U19 AI110820
6 · The paper itself

Abstract

backgroundEnterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines centered on the classical canonical antigens, the colonization factors and heat-labile toxin. Two non-canonical ETEC antigens, the EtpA adhesin, and the EatA mucinase are immunogenic in humans and protective in animal models. To foster rational vaccine design that complements existing strategies, we examined the distribution and molecular conservation of these antigens in a diverse population of ETEC isolates.

methodsGeographically diverse ETEC isolates (n = 1159) were interrogated by PCR, immunoblotting, and/or whole genome sequencing (n = 46) to examine antigen conservation. The most divergent proteins were purified and their core functions assessed in vitro.

resultsEatA and EtpA or their coding sequences were present in 57.0% and 51.5% of the ETEC isolates overall, respectively; and were globally dispersed without significant regional differences in antigen distribution. These antigens also exhibited >93% amino acid sequence identity with even the most divergent proteins retaining the core adhesin and mucinase activity assigned to the prototype molecules.

conclusionsEtpA and EatA are well-conserved molecules in the ETEC pathovar, suggesting that they serve important roles in virulence and that they could be exploited for rational vaccine design.

Indexed as

Genetic VariationAntigens, BacterialEnterotoxigenic Escherichia coliEscherichia coli InfectionsEscherichia coli ProteinsGlobal HealthHumansImmunoblottingMembrane GlycoproteinsPeptide HydrolasesPolymerase Chain ReactionWhole Genome SequencingAntigens, BacterialEatA protein, E coliEscherichia coli ProteinsEtpA protein, E coliMembrane GlycoproteinsPeptide Hydrolases

Identifiers

PMID31756188
PMCPMC6897418
OpenAlexW2991394462

What OpenQuestion holds

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LicenceCC BY
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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.