Evidence map›Paper›PMID 26346926›Full record

ArticleScientific reports2015

A whole-genome RNAi screen uncovers a novel role for human potassium channels in cell killing by the parasite Entamoeba histolytica.

Chelsea Marie, Hans P Verkerke, Dan Theodorescu, William A Petri

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025
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  7. Gasdermins in Innate Host Defense AgainstFrontiers in immunology · 2022
    Review
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  11. Review
  12. Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action.Microbiology and molecular biology reviews : MMBR · 2018
    Review
  13. Article
  14. Article
  15. Review
  16. 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

4 authors at 2 institutions in 1 country.

Chelsea MarieDivision of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia USA.
Hans P VerkerkeDivision of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia USA.
Dan TheodorescuDepartment of Surgery, Department of Pharmacology, University of Colorado Comprehensive Cancer Center, University of Colorado, Denver, CO, USA.
William A PetriDivision of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia USA.
University of Virginia · USUniversity of Colorado Cancer Center · US

Funding

Regulation and Targeting of CD24 in Bladder CancerR01CA075115 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI THEODORESCU, DAN · 2003 to 2024
$7.0M
STRUCTURE/FUNCTION OF E HISTOLYTICA ADHERENCE LECTINR01AI026649 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI PETRI, WILLIAM A · 1989 to 2016
$6.1M
Role of CREM in Amebic Colitis and Inflammatory Bowel DiseaseR37AI026649 · NIAID · UNIVERSITY OF VIRGINIA · PI William A Petri · 2018 to 2026
$5.0M
Understanding the RhoGDI2 metastasis suppressor geneR01CA143971 · NCI · UNIVERSITY OF COLORADO DENVER · PI THEODORESCU, DAN · 2010 to 2020
$4.4M
MECHANISMS OF BLADDER CANCER INVANSIONR29CA075115 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI THEODORESCU, DAN · 1997 to 2001
$217k
NCI NIH HHS CA075115NCI NIH HHS CA143971NCI NIH HHS R01 CA075115NCI NIH HHS R01 CA143971NCI NIH HHS R29 CA075115NIAID NIH HHS F32AI09304NIAID NIH HHS R01 AI026649NIAID NIH HHS R01AI026649NIAID NIH HHS R37 AI026649
6 · The paper itself

Abstract

The parasite Entamoeba histolytica kills human cells resulting in ulceration, inflammation and invasion of the colonic epithelium. We used the cytotoxic properties of ameba to select a genome-wide RNAi library to reveal novel host factors that control susceptibility to amebic killing. We identified 281 candidate susceptibility genes and bioinformatics analyses revealed that ion transporters were significantly enriched among susceptibility genes. Potassium (K(+)) channels were the most common transporter identified. Their importance was further supported by colon biopsy of humans with amebiasis that demonstrated suppressed K(+) channel expression. Inhibition of human K(+) channels by genetic silencing, pharmacologic inhibitors and with excess K(+) protected diverse cell types from E. histolytica-induced death. Contact with E. histolytica parasites triggered K(+) channel activation and K(+) efflux by intestinal epithelial cells, which preceded cell killing. Specific inhibition of Ca(2+)-dependent K(+) channels was highly effective in preventing amebic cytotoxicity in intestinal epithelial cells and macrophages. Blockade of K(+) efflux also inhibited caspase-1 activation, IL-1β secretion and pyroptotic death in THP-1 macrophages. We concluded that K(+) channels are host mediators of amebic cytotoxicity in multiple cells types and of inflammasome activation in macrophages.

Indexed as

Genome-Wide Association StudyGenomicsRNA InterferenceAnimalsCell LineComputational BiologyEntamoeba histolyticaEpithelial CellsGene Expression RegulationGene LibraryHigh-Throughput Nucleotide SequencingHigh-Throughput Screening AssaysHost-Parasite InteractionsHumansInflammasomesIon TransportInflammasomesMicroRNAsPotassium Channel BlockersPotassium Channels

Identifiers

PMID26346926
PMCPMC4561901
OpenAlexW2408766557

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.