ArticleNature communications2021
Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues.
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 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
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- Development of Peptide Glucosyltransferase Inhibitors With Comprehensive Coverage Across Clostridioides difficile Toxin B Sub-Types.Biotechnology and bioengineering · 2026Article
- Performance evaluation of the QIAstat-Dx gastrointestinal panel 2 for the detection ofJournal of clinical microbiology · 2025Article
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- Synthetic niclosamide-loaded controlled-release nanospheres with high solubility and stability exerting multiple effects againstFrontiers in microbiology · 2025Article
- Gut microbiota modulation in gastrointestinal disorders: current evidence and therapeutic perspectives.Frontiers in cellular and infection microbiology · 2025Review
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- Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells.Communications biology · 2023Article
- The Hospital Environment as a Potential Source forInternational journal of environmental research and public health · 2023Article
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- Stereoselective Synthesis of Nojirimycin α-ACS omega · 2022Article
- Discovery of a novel natural product inhibitor of Clostridioides difficile with potent activity in vitro and in vivo.PloS one · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Clostridium difficile causes life-threatening diarrhea and is the leading cause of healthcare-associated bacterial infections in the United States. TcdA and TcdB bacterial toxins are primary determinants of disease pathogenesis and are attractive therapeutic targets. TcdA and TcdB contain domains that use UDP-glucose to glucosylate and inactivate host Rho GTPases, resulting in cytoskeletal changes causing cell rounding and loss of intestinal integrity. Transition state analysis revealed glucocationic character for the TcdA and TcdB transition states. We identified transition state analogue inhibitors and characterized them by kinetic, thermodynamic and structural analysis. Iminosugars, isofagomine and noeuromycin mimic the transition state and inhibit both TcdA and TcdB by forming ternary complexes with Tcd and UDP, a product of the TcdA- and TcdB-catalyzed reactions. Both iminosugars prevent TcdA- and TcdB-induced cytotoxicity in cultured mammalian cells by preventing glucosylation of Rho GTPases. Iminosugar transition state analogues of the Tcd toxins show potential as therapeutics for C. difficile pathology.
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Registered trials
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