ArticlePLoS pathogens2021
Functional analyses of epidemic Clostridioides difficile toxin B variants reveal their divergence in utilizing receptors and inducing pathology.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 41 citations in OpenAlex.
- Diversity and evolution of leukotoxin operons inmSystems · 2026Article
- CD44 is a macrophage receptor for TcdB fromGut microbes · 2025Article
- The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice.PLoS pathogens · 2025Article
- History and Evolution of the HypervirulentMicroorganisms · 2025Review
- De novo design of potent inhibitors of clostridial family toxins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- AgainstToxins · 2025Review
- Review
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation.Cell discovery · 2024Article
- De novo design of mini-protein binders broadly neutralizing Clostridioides difficile toxin B variants.Nature communications · 2024Article
- A sequence invariable region in TcdB2 is required for toxin escape fromJournal of bacteriology · 2024Article
- Genomic and phenotypic studies amongMicrobiology spectrum · 2024Article
- Identification of a hemorrhagic determinant inMicrobiology spectrum · 2024Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- CSPG4-dependent cytotoxicity formSphere · 2024Article
- Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin.Nature communications · 2024Article
- Advances in diagnostic assays forFrontiers in cellular and infection microbiology · 2024Review
- Genomic and phenotypic characterization of aFrontiers in cellular and infection microbiology · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Host Immunity and Immunization Strategies for Clostridioides difficile Infection.Clinical microbiology reviews · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridioides difficile toxin B (TcdB) is a key virulence factor that causes C. difficile associated diseases (CDAD) including diarrhea and pseudomembranous colitis. TcdB can be divided into multiple subtypes/variants based on their sequence variations, of which four (TcdB1-4) are dominant types found in major epidemic isolates. Here, we find that these variants are highly diverse in their receptor preference: TcdB1 uses two known receptors CSPG4 and Frizzled (FZD) proteins, TcdB2 selectively uses CSPG4, TcdB3 prefers to use FZDs, whereas TcdB4 uses neither CSPG4 nor FZDs. By creating chimeric toxins and systematically switching residues between TcdB1 and TcdB3, we determine that regions in the N-terminal cysteine protease domain (CPD) are involved in CSPG4-recognition. We further evaluate the pathological effects induced by TcdB1-4 with a mouse intrarectal installation model. TcdB1 leads to the most severe overall symptoms, followed by TcdB2 and TcdB3. When comparing the TcdB2 and TcdB3, TcdB2 causes stronger oedema while TcdB3 induces severer inflammatory cell infiltration. These findings together demonstrate divergence in the receptor preference and further lead to colonic pathology for predominant TcdB subtypes.
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