ArticleNature communications2021
Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled 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.
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Tandem-repeat lectins: structural and functional insights.Glycobiology · 2024Pooled it
- From colonization to infection: Genomic evolution of Clostridioides difficile pathogenesis.Cell reports · 2026Review
- Substance P receptor blockade is associated with increased survival of patients withbioRxiv : the preprint server for biology · 2026Article
- The impact of TcdB conformational dynamics on vaccination against Clostridioides difficile.PLoS pathogens · 2026Article
- Integrating machine learning and WGCNA to identify core candidate genes and decipher immune-related molecular networks in TcdA/TcdB-associated CDI.Antonie van Leeuwenhoek · 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
- Article
- Development of Peptide Glucosyltransferase Inhibitors With Comprehensive Coverage Across Clostridioides difficile Toxin B Sub-Types.Biotechnology and bioengineering · 2026Article
- Toxic Megacolon With a Positive Clostridioides difficile Antigen but Negative Toxin Assay.Cureus · 2026Article
- A single amino acid substitution determines susceptibility ofFrontiers in cellular and infection microbiology · 2026Article
- Immune Aspects of Clostridioides difficile Infection and Vaccine Development.Infectious disease clinics of North America · 2025Review
- Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin.Nature microbiology · 2025Article
- The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice.PLoS pathogens · 2025Article
- Unravelling three-way interactions betweenJournal of medical microbiology · 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
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- Clostridioides difficile meets the adenosine system: the art of manipulating host homeostasis.Journal of biomedical science · 2025Review
- AgainstToxins · 2025Review
- MappingmBio · 2025Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
C. difficile is a major cause of antibiotic-associated gastrointestinal infections. Two C. difficile exotoxins (TcdA and TcdB) are major virulence factors associated with these infections, and chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for TcdB, but its pathophysiological relevance and the molecular details that govern recognition remain unknown. Here, we determine the cryo-EM structure of a TcdB-CSPG4 complex, revealing a unique binding site spatially composed of multiple discontinuous regions across TcdB. Mutations that selectively disrupt CSPG4 binding reduce TcdB toxicity in mice, while CSPG4-knockout mice show reduced damage to colonic tissues during C. difficile infections. We further show that bezlotoxumab, the only FDA approved anti-TcdB antibody, blocks CSPG4 binding via an allosteric mechanism, but it displays low neutralizing potency on many TcdB variants from epidemic hypervirulent strains due to sequence variations in its epitopes. In contrast, a CSPG4-mimicking decoy neutralizes major TcdB variants, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.
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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.