Evidence map›Paper›PMID 23958904›Full record

ArticleVirulence2013

The micronutrient zinc inhibits EAEC strain 042 adherence, biofilm formation, virulence gene expression, and epithelial cytokine responses benefiting the infected host.

Pedro Medeiros, David T Bolick, James K Roche, Francisco Noronha, Caio Pinheiro, Glynis L Kolling, Aldo Lima, Richard L Guerrant

Open access · goldAbstract read
In one paragraph

Article in Virulence, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Isotopically enrichedScientific reports · 2026
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  4. Is Oral Vaccination againstAnimals : an open access journal from MDPI · 2023
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  10. Iron Reshapes the Gut Microbiome and Host Metabolism.Journal of lipid and atherosclerosis · 2021
    Review
  11. Review
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  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Gastroenterology and hepatology from bed to bench · 2017
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 3 countries.

Pedro MedeirosCenter for Global Health; Division of Infectious Diseases and International Health; School of Medicine; University of Virginia; Charlottesville, VA USA; Institute of Biomedicine; Federal University of Ceará; Fortaleza, CE Brazil.
David T Bolick
James K Roche
Francisco Noronha
Caio Pinheiro
Glynis L Kolling
Aldo Lima
Richard L Guerrant
Office of Infectious Diseases · USUniversity of Virginia · USCenter for Global Health · USIndiana University School of MedicineInstitute for Biomedicine · ITUniversidade de Fortaleza · BR

Funding

Vaccine strategy for broad spectrum protection agains non-typhoidal salmonellU54AI057168 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 2003 to 2013
$91.5M
Global Infectious Disease Research Training Program at UVAD43TW006578 · FIC · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUERRANT, RICHARD L · 2003 to 2018
$2.7M
FIC NIH HHS D43 TW006578FIC NIH HHS D43TW006578NIAID NIH HHS U54 AI057168NIAID NIH HHS U54 AI57168
6 · The paper itself

Abstract

Enteroaggregative Escherichia coli (EAEC) is a major pathogen worldwide, associated with diarrheal disease in both children and adults, suggesting the need for new preventive and therapeutic treatments. We investigated the role of the micronutrient zinc in the pathogenesis of an E. coli strain associated with human disease. A variety of bacterial characteristics-growth in vitro, biofilm formation, adherence to IEC-6 epithelial cells, gene expression of putative EAEC virulence factors as well as EAEC-induced cytokine expression by HCT-8 cells-were quantified. At concentrations (≤ 0.05 mM) that did not alter EAEC growth (strain 042) but that are physiologic in serum, zinc markedly decreased the organism's ability to form biofilm (P<0.001), adhere to IEC-6 epithelial cells (P<0.01), and express putative EAEC virulence factors (aggR, aap, aatA, virK) (P<0.03). After exposure of the organism to zinc, the effect on virulence factor generation was prolonged (> 3 h). Further, EAEC-induced IL-8 mRNA and protein secretion by HCT-8 epithelial cells were significantly reduced by 0.05 mM zinc (P<0.03). Using an in vivo murine model of diet-induced zinc-deficiency, oral zinc supplementation (0.4 µg/mouse daily) administered after EAEC challenge (10 (10) CFU/mouse) significantly abrogated growth shortfalls (by>90%; P<0.01); furthermore, stool shedding was reduced (days 9-11) but tissue burden of organisms in the intestine was unchanged. These findings suggest several potential mechanisms whereby physiological levels of zinc alter pathogenetic events in the bacterium (reducing biofilm formation, adherence to epithelium, virulence factor expression) as well as the bacterium's effect on the epithelium (cytokine response to exposure to EAEC) to alter EAEC pathogenesis in vitro and in vivo. These effects may help explain and extend the benefits of zinc in childhood diarrhea and malnutrition.

Indexed as

AdultAnimalsAnti-Bacterial AgentsBacterial AdhesionBacterial LoadBacterial SheddingBiofilmsCell LineChildChild, PreschoolCytokinesDisease Models, AnimalEpithelial CellsEscherichia coliEscherichia coli InfectionsGene Expression Regulation, BacterialAnti-Bacterial AgentsCytokinesMicronutrientsZincbiofilmEAECE. colimalnutritionvirulence factorszinc

Identifiers

PMID23958904
PMCPMC3906296
OpenAlexW2152544601

What OpenQuestion holds

Textmetadata
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.