ArticleScience translational medicine2015
A small-molecule antivirulence agent for treating Clostridium difficile infection.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 138 citations in OpenAlex.
- Design and Synthesis of Phosphonoproline-Proline Bioisosteric Mimetics of Proline Dimers: Pseudopeptide Constructs as Potential Inhibitors of the Zn-Metalloprotease PPEP‑1 Associated withACS medicinal chemistry letters · 2026Article
- Evaluation of the antibacterial activity of the natural product α-mangostin against Clostridioides difficile.PloS one · 2026Article
- Caffeic acid phenethyl ester protectseLife · 2025Article
- Allosterically switchable network orientsProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Loratadine as an Anti-inflammatory Agent Against Clostridium difficile Toxin B.The Journal of infectious diseases · 2024Article
- Review
- Article
- Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning.Frontiers in pharmacology · 2024Review
- Ebselen: A Promising Repurposing Drug to Treat Infections Caused by Multidrug-Resistant Microorganisms.Interdisciplinary perspectives on infectious diseases · 2024Review
- Biofilm Formation ofMicroorganisms · 2023Review
- Article
- Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action.Journal of medicinal chemistry · 2023Article
- Antibacterial Activity of Ebselen.International journal of molecular sciences · 2023Review
- Article
- Clostridioides difficile toxins: mechanisms of action and antitoxin therapeutics.Nature reviews. Microbiology · 2022Review
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Host and Clostridioides difficile-Response Modulated by Micronutrients and Glutamine: An Overview.Frontiers in nutrition · 2022Review
- Article
- Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues.Nature communications · 2021Article
- Ebselen Not Only Inhibits Clostridioides difficile Toxins but Displays Redox-Associated Cellular Killing.Microbiology spectrum · 2021Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Clostridium difficile infection (CDI) is a worldwide health threat that is typically triggered by the use of broad-spectrum antibiotics, which disrupt the natural gut microbiota and allow this Gram-positive anaerobic pathogen to thrive. The increased incidence and severity of disease coupled with decreased response, high recurrence rates, and emergence of multiple antibiotic-resistant strains have created an urgent need for new therapies. We describe pharmacological targeting of the cysteine protease domain (CPD) within the C. difficile major virulence factor toxin B (TcdB). Through a targeted screen with an activity-based probe for this protease domain, we identified a number of potent CPD inhibitors, including one bioactive compound, ebselen, which is currently in human clinical trials for a clinically unrelated indication. This drug showed activity against both major virulence factors, TcdA and TcdB, in biochemical and cell-based studies. Treatment in a mouse model of CDI that closely resembles the human infection confirmed a therapeutic benefit in the form of reduced disease pathology in host tissues that correlated with inhibition of the release of the toxic glucosyltransferase domain (GTD). Our results show that this non-antibiotic drug can modulate the pathology of disease and therefore could potentially be developed as a therapeutic for the treatment of CDI.
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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.