Evidence map›Paper›PMID 22522680›Full record

ArticleApplied and environmental microbiology2012

Precise manipulation of the Clostridium difficile chromosome reveals a lack of association between the tcdC genotype and toxin production.

Stephen T Cartman, Michelle L Kelly, Daniela Heeg, John T Heap, Nigel P Minton

Open access · bronzeAbstract read
In one paragraph

Article in Applied and environmental microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
12.4field-weighted citation impact, top 1% 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

142 citing papers in PubMed, 240 citations in OpenAlex.

  1. A set of genetic tools for use inMicrobiology (Reading, England) · 2026
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  4. Nanoluciferase-Based Reporters for Clostridioides difficile.Methods in molecular biology (Clifton, N.J.) · 2026
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  7. iScience · 2025
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  18. Genomic and phenotypic characterization of aFrontiers in cellular and infection microbiology · 2024
    Article
  19. Ribotypes and New Virulent Strains Across Europe.Advances in experimental medicine and biology · 2024
    Review
  20. Biofilm Formation ofMicroorganisms · 2023
    Review

82 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Stephen T CartmanClostridia Research Group, Centre for Biomolecular Sciences, School of Molecular Medical Sciences, Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, The University of Nottingham, University Park, United Kingdom. stephen.cartman@nottingham.ac.uk
Michelle L Kelly
Daniela Heeg
John T Heap
Nigel P Minton
University of Nottingham · GBNIHR Nottingham Digestive Diseases Biomedical Research Unit · GB

Funding

Biotechnology and Biological Sciences Research Council BB/G016224/1Medical Research Council G0601176
6 · The paper itself

Abstract

Clostridium difficile causes a potentially fatal diarrheal disease through the production of its principal virulence factors, toxin A and toxin B. The tcdC gene is thought to encode a negative regulator of toxin production. Therefore, increased toxin production, and hence increased virulence, is often inferred in strains with an aberrant tcdC genotype. This report describes the first allele exchange system for precise genetic manipulation of C. difficile, using the codA gene of Escherichia coli as a heterologous counterselection marker. It was used to systematically restore the Δ117 frameshift mutation and the 18-nucleotide deletion that occur naturally in the tcdC gene of C. difficile R20291 (PCR ribotype 027). In addition, the naturally intact tcdC gene of C. difficile 630 (PCR ribotype 012) was deleted and then subsequently restored with a silent nucleotide substitution, or "watermark," so the resulting strain was distinguishable from the wild type. Intriguingly, there was no association between the tcdC genotype and toxin production in either C. difficile R20291 or C. difficile 630. Therefore, an aberrant tcdC genotype does not provide a broadly applicable rationale for the perceived notion that PCR ribotype 027 strains are "high-level" toxin producers. This may well explain why several studies have reported that an aberrant tcdC gene does not predict increased toxin production or, indeed, increased virulence.

Indexed as

Bacterial ProteinsBacterial ToxinsClostridioides difficileDNA, BacterialEscherichia coliFrameshift MutationGene DeletionGenetics, MicrobialGenotypeMolecular Sequence DataMutagenesis, InsertionalRecombination, GeneticRepressor ProteinsSequence Analysis, DNABacterial ProteinsBacterial ToxinsDNA, BacterialRepressor ProteinsTcdC protein, Clostridium difficile

Identifiers

PMID22522680
PMCPMC3370502
OpenAlexW2110146873

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.