Evidence map›Paper›PMID 25047848›Full record

ArticleInfection and immunity2014

The HtrA-like protease CD3284 modulates virulence of Clostridium difficile.

Dennis Bakker, Anthony M Buckley, Anne de Jong, Vincent J C van Winden, Joost P A Verhoeks, Oscar P Kuipers, Gillian R Douce, Ed J Kuijper, Wiep Klaas Smits, Jeroen Corver

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Analysis of essential genes inJournal of bacteriology · 2025
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  4. Frontiers in microbiology · 2024
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  8. CRISPR Genome Editing Systems in the GenusJournal of bacteriology · 2019
    Review
  9. Protease Activity ofFrontiers in cellular and infection microbiology · 2019
    Article
  10. Function of Serine Protease HtrA in the Lifecycle of the Foodborne PathogenEuropean journal of microbiology & immunology · 2018
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. 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

10 authors at 3 institutions in 2 countries.

Dennis BakkerDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands.
Anthony M BuckleyInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Anne de JongDepartment of Molecular Genetics, University of Groningen, Groningen, The Netherlands.
Vincent J C van WindenDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands.
Joost P A VerhoeksDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands.
Oscar P KuipersDepartment of Molecular Genetics, University of Groningen, Groningen, The Netherlands.
Gillian R DouceInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Ed J KuijperDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands.
Wiep Klaas SmitsDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands W.K.Smits@LUMC.nl J.corver@LUMC.nl.
Jeroen CorverDepartment of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands W.K.Smits@LUMC.nl J.corver@LUMC.nl.
Leiden University Medical Center · NLUniversity of Glasgow · GBUniversity of Groningen · NL

Funding

Wellcome TrustWellcome Trust 086418
6 · The paper itself

Abstract

In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis. Besides the two main virulence factors toxin A and toxin B, other virulence factors are likely to play a role in the pathogenesis of the disease. In other Gram-positive and Gram-negative pathogenic bacteria, conserved high-temperature requirement A (HtrA)-like proteases have been shown to have a role in protein homeostasis and quality control. This affects the functionality of virulence factors and the resistance of bacteria to (host-induced) environmental stresses. We found that the C. difficile 630 genome encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its role in vivo and in vitro through the creation of an isogenic ClosTron-based htrA mutant of C. difficile strain 630Δerm (wild type). In contrast to the attenuated phenotype seen with htrA deletion in other pathogens, this mutant showed enhanced virulence in the Golden Syrian hamster model of acute C. difficile infection. Microarray data analysis showed a pleiotropic effect of htrA on the transcriptome of C. difficile, including upregulation of the toxin A gene. In addition, the htrA mutant showed reduced spore formation and adherence to colonic cells. Together, our data show that htrA can modulate virulence in C. difficile.

Indexed as

AnimalsBacterial AdhesionCaco-2 CellsClostridioides difficileClostridium InfectionsCricetinaeDisease Models, AnimalEpithelial CellsFemaleGene DeletionGene Expression ProfilingHumansMesocricetusMicroarray AnalysisPeptide HydrolasesVirulencePeptide HydrolasesVirulence Factors

Identifiers

PMID25047848
PMCPMC4187886
OpenAlexW2143833297

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.