ArticleProceedings of the National Academy of Sciences of the United States of America2015
Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
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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.
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Who cites it
105 citing papers in PubMed, 168 citations in OpenAlex.
- From colonization to infection: Genomic evolution of Clostridioides difficile pathogenesis.Cell reports · 2026Review
- Balancing act of cytokines in controlling the severity ofInfection and immunity · 2026Review
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- 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
- Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026Review
- CD44 is a macrophage receptor for TcdB fromGut microbes · 2025Article
- Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary Clostridioides difficile Isolates.The Journal of infectious diseases · 2025Article
- Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.Molecular biotechnology · 2025Review
- 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
- Clostridioides difficile meets the adenosine system: the art of manipulating host homeostasis.Journal of biomedical science · 2025Review
- AgainstToxins · 2025Review
- MappingmBio · 2025Article
- Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- A sequence invariable region in TcdB2 is required for toxin escape fromJournal of bacteriology · 2024Article
- Identification of a hemorrhagic determinant inMicrobiology spectrum · 2024Article
- Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- CSPG4-dependent cytotoxicity formSphere · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Clostridium difficile is the leading cause of hospital-acquired diarrhea in the United States. The two main virulence factors of C. difficile are the large toxins, TcdA and TcdB, which enter colonic epithelial cells and cause fluid secretion, inflammation, and cell death. Using a gene-trap insertional mutagenesis screen, we identified poliovirus receptor-like 3 (PVRL3) as a cellular factor necessary for TcdB-mediated cytotoxicity. Disruption of PVRL3 expression by gene-trap mutagenesis, shRNA, or CRISPR/Cas9 mutagenesis resulted in resistance of cells to TcdB. Complementation of the gene-trap or CRISPR mutants with PVRL3 resulted in restoration of TcdB-mediated cell death. Purified PVRL3 ectodomain bound to TcdB by pull-down. Pretreatment of cells with a monoclonal antibody against PVRL3 or prebinding TcdB to PVRL3 ectodomain also inhibited cytotoxicity in cell culture. The receptor is highly expressed on the surface epithelium of the human colon and was observed to colocalize with TcdB in both an explant model and in tissue from a patient with pseudomembranous colitis. These data suggest PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection.
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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.