ArticleNature medicine2011
Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03926741 (Methods to Identify and Treat Severe Asthma Patients Project 1), which is not on this map. Cited by 54 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.
Methods to Identify and Treat Severe Asthma Patients Project 1: GSNOR Phenotyping and GSNO Challenge
Who cites it
54 citing papers in PubMed, 91 citations in OpenAlex.
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- Endogenous Symmetric Dimethylarginine (SDMA) and Asymmetrical Dimethylarginine (ADMA) Levels in Healthy Cows and Cows with Subclinical and Clinical Mastitis-A Comparative Study.Animals : an open access journal from MDPI · 2025Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens.Nature communications · 2024Article
- Host Immunity and Immunization Strategies for Clostridioides difficile Infection.Clinical microbiology reviews · 2023Review
- ThemBio · 2022Article
- Translational Aspects of the Immunology of Clostridioides difficile Infection: Implications for Pediatric Populations.Journal of the Pediatric Infectious Diseases Society · 2021Review
- Large Clostridial Toxins: Mechanisms and Roles in Disease.Microbiology and molecular biology reviews : MMBR · 2021Review
- S-nitrosylation-mediated coupling of G-protein alpha-2 with CXCR5 induces Hippo/YAP-dependent diabetes-accelerated atherosclerosis.Nature communications · 2021Article
- Host Immune Responses toFrontiers in microbiology · 2021Review
- Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling.Gastroenterology · 2020Article
- S-nitrosylation-mediated activation of a histidine kinase represses the type 3 secretion system and promotes virulence of an enteric pathogen.Nature communications · 2020Article
- Protein S-Nitrosylation: Determinants of Specificity and Enzymatic Regulation of S-Nitrosothiol-Based Signaling.Antioxidants & redox signaling · 2019Review
- Article
- S-Nitrosoglutathione formation at gastric pH is augmented by ascorbic acid and by the antioxidant vitamin complex, Resiston.Pharmaceutical biology · 2018Article
- Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.Critical care (London, England) · 2018Article
- Treatment of Clostridium difficile Infection with a Small-Molecule Inhibitor of Toxin UDP-Glucose Hydrolysis Activity.Antimicrobial agents and chemotherapy · 2018Article
- Clostridium difficile Infection and the Tangled Web of Interactions Among Host, Pathogen, and Microbiota.Gastroenterology · 2018Article
- Ceragenin CSA13 Reduces Clostridium difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites.Gastroenterology · 2018Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
The global prevalence of severe Clostridium difficile infection highlights the profound clinical significance of clostridial glucosylating toxins. Virulence is dependent on the autoactivation of a toxin cysteine protease, which is promoted by the allosteric cofactor inositol hexakisphosphate (InsP(6)). Host mechanisms that protect against such exotoxins are poorly understood. It is increasingly appreciated that the pleiotropic functions attributed to nitric oxide (NO), including host immunity, are in large part mediated by S-nitrosylation of proteins. Here we show that C. difficile toxins are S-nitrosylated by the infected host and that S-nitrosylation attenuates virulence by inhibiting toxin self-cleavage and cell entry. Notably, InsP(6)- and inositol pyrophosphate (InsP(7))-induced conformational changes in the toxin enabled host S-nitrosothiols to transnitrosylate the toxin catalytic cysteine, which forms part of a structurally conserved nitrosylation motif. Moreover, treatment with exogenous InsP(6) enhanced the therapeutic actions of oral S-nitrosothiols in mouse models of C. difficile infection. Allostery in bacterial proteins has thus been successfully exploited in the evolutionary development of nitrosothiol-based innate immunity and may provide an avenue to new therapeutic approaches.
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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.