ArticleNature communications2022
Identification of TFPI as a receptor reveals recombination-driven receptor switching in Clostridioides difficile toxin B variants.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening.Biochemical Society transactions · 2026Review
- Diversity and evolution of leukotoxin operons inmSystems · 2026Article
- CSPG4 Mediates Inflammatory, Cell Death, and Senescence Responses in Enteric Glia Exposed to Clostridioides difficile Toxins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The interplay between host immunity andmBio · 2025Review
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- Design, performance, processing, and validation of a pooled CRISPR perturbation screen for bacterial toxins.Nature protocols · 2025Review
- AgainstToxins · 2025Review
- Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.Nature communications · 2024Article
- Identification of a hemorrhagic determinant inMicrobiology spectrum · 2024Article
- Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin.Nature communications · 2024Article
- Article
- Structural dynamics of the CROPs domain control stability and toxicity of Paeniclostridium sordellii lethal toxin.Nature communications · 2023Article
- Gaining New Insights into Fundamental Biological Pathways by Bacterial Toxin-Based Genetic Screens.Bioengineering (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
Toxin B (TcdB) is a major exotoxin responsible for diseases associated with Clostridioides difficile infection. Its sequence variations among clinical isolates may contribute to the difficulty in developing effective therapeutics. Here, we investigate receptor-binding specificity of major TcdB subtypes (TcdB1 to TcdB12). We find that representative members of subtypes 2, 4, 7, 10, 11, and 12 do not recognize the established host receptor, frizzled proteins (FZDs). Using a genome-wide CRISPR-Cas9-mediated screen, we identify tissue factor pathway inhibitor (TFPI) as a host receptor for TcdB4. TFPI is recognized by a region in TcdB4 that is homologous to the FZD-binding site in TcdB1. Analysis of 206 TcdB variant sequences reveals a set of six residues within this receptor-binding site that defines a TFPI binding-associated haplotype (designated B4/B7) that is present in all TcdB4 members, a subset of TcdB7, and one member of TcdB2. Intragenic micro-recombination (IR) events have occurred around this receptor-binding region in TcdB7 and TcdB2 members, resulting in either TFPI- or FZD-binding capabilities. Introduction of B4/B7-haplotype residues into TcdB1 enables dual recognition of TFPI and FZDs. Finally, TcdB10 also recognizes TFPI, although it does not belong to the B4/B7 haplotype, and shows species selectivity: it recognizes TFPI of chicken and to a lesser degree mouse, but not human, dog, or cattle versions. These findings identify TFPI as a TcdB receptor and reveal IR-driven changes on receptor-specificity among TcdB variants.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.