• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Cysteine Protease-Mediated Autocleavage of Clostridium difficile Toxins Regulates Their Proinflammatory Activity

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Publisher version
    View Source
    Access full-text PDFOpen Access
    View Source
    Check access options
    Check access options
    Author
    Zhang, Y.
    Li, S.
    Yang, Z.
    Date
    2018
    Journal
    Cellular and Molecular Gastroenterology and Hepatology
    Publisher
    Elsevier Inc
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1016/j.jcmgh.2018.01.022
    Abstract
    Background & Aims: Clostridium difficile toxin A (TcdA) and C difficile toxin toxin B (TcdB), the major virulence factors of the bacterium, cause intestinal tissue damage and inflammation. Although the 2 toxins are homologous and share a similar domain structure, TcdA is generally more inflammatory whereas TcdB is more cytotoxic. The functional domain of the toxins that govern the proinflammatory activities of the 2 toxins is unknown. Methods: Here, we investigated toxin domain functions that regulate the proinflammatory activity of C difficile toxins. By using a mouse ilea loop model, human tissues, and immune cells, we examined the inflammatory responses to a series of chimeric toxins or toxin mutants deficient in specific domain functions. Results: Blocking autoprocessing of TcdB by mutagenesis or chemical inhibition, while reducing cytotoxicity of the toxin, significantly enhanced its proinflammatory activities in the animal model. Furthermore, a noncleavable mutant TcdB was significantly more potent than the wild-type toxin in the induction of proinflammatory cytokines in human colonic tissues and immune cells. Conclusions: In this study, we identified a novel mechanism of regulating the biological activities of C difficile toxins in that cysteine protease-mediated autoprocessing regulates toxins' proinflammatory activities. Our findings provide new insight into the pathogenesis of C difficile infection and the design of therapeutics against the disease. Copyright 2018 The Authors
    Keyword
    Autoprocessing
    C difficile
    Cysteine Protease
    Inflammation
    Toxins
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044960204&doi=10.1016%2fj.jcmgh.2018.01.022&partnerID=40&md5=d1659abf9bbcf309f0a2982536a14136; http://hdl.handle.net/10713/9384
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jcmgh.2018.01.022
    Scopus Count
    Collections
    UMB Open Access Articles 2018

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.