Evidence map›Paper›PMID 16926402›Full record

ArticleInfection and immunity2006

Uropathogenic Escherichia coli induces extrinsic and intrinsic cascades to initiate urothelial apoptosis.

David J Klumpp, Matthew T Rycyk, Michael C Chen, Praveen Thumbikat, Shomit Sengupta, Anthony J Schaeffer

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

53 citing papers in PubMed, 97 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

David J KlumppDepartment of Urology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA. d-klumpp@northwestern.edu
Matthew T Rycyk
Michael C Chen
Praveen Thumbikat
Shomit Sengupta
Anthony J Schaeffer
Northwestern University · US

Funding

NIDDK NIH HHS R01 DK 04648
6 · The paper itself

Abstract

A murine model of urinary tract infection identified urothelial apoptosis as a key event in the pathogenesis mediated by uropathogenic Escherichia coli (UPEC), yet the mechanism of this important host response is not well characterized. We employed a culture model of UPEC-urothelium interactions to examine the biochemical events associated with urothelial apoptosis induced by the UPEC strain NU14. NU14 induced DNA cleavage within 5 h that was inhibited by the broad caspase inhibitor ZVAD, and urothelial caspase 3 activity was induced within 3 h of exposure to type 1 piliated NU14 and was dependent upon interactions mediated by the type 1 pilus adhesin FimH. Flow cytometry experiments using chloromethyl-X-rosamine and Indo-1 revealed FimH-dependent mitochondrial membrane depolarization and elevated [Ca(2+)](in), respectively, indicating activation of the intrinsic apoptotic pathway. Consistent with this possibility, overexpression of Bcl(XL) inhibited NU14 activation of caspase 3. Immunoblotting, caspase inhibitors, and caspase activity assays implicated both caspase 2 and caspase 8 in apoptosis, suggesting the involvement of the intrinsic and extrinsic apoptotic cascades. To reconcile the apparent activation of both extrinsic and intrinsic pathways, we examined Bid-green fluorescent protein localization and observed translocation from the cytosol to mitochondria in response to either NU14 or purified FimH. These data suggest that FimH acts as a tethered toxin of UPEC that activates caspase-dependent urothelial apoptosis via direct induction of the extrinsic pathway and that the intrinsic pathway is activated indirectly as a result of coupling by caspase 8-mediated Bid cleavage.

Indexed as

ApoptosisBacterial AdhesionAdhesins, Escherichia colibcl-X ProteinBH3 Interacting Domain Death Agonist ProteinCalciumCaspase 2Caspase 8Caspase InhibitorsCaspasesCells, CulturedCysteine Proteinase InhibitorsEscherichia coliEscherichia coli InfectionsFimbriae ProteinsFlow CytometryAdhesins, Escherichia coliBCL2L1 protein, humanbcl-X ProteinBH3 Interacting Domain Death Agonist ProteinCalciumCASP8 protein, humanCaspase 2Caspase 8Caspase InhibitorsCaspasesCysteine Proteinase InhibitorsFimbriae ProteinsfimH protein, E coli

Identifiers

PMID16926402
PMCPMC1594819
OpenAlexW1968464040

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.