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  • Autocatalytic cleavage of Clostridium difficile toxin B
    Reineke, Jessica ...
    Clostridium difficile, the causative agent of nosocomial antibiotic-associateddiarrhoea and pseudomembranous colitis, possesses two main virulence factors: the large clostridial cytotoxins A and B. ... It has been proposed that toxin B is cleaved by a cytosolic factor of the eukaryotic target cell during its cellular uptake. Here we report that cleavage of not only toxin B, but also all other large clostridial cytotoxins, is an autocatalytic process dependent on host cytosolic inositolphosphate cofactors.A covalent inhibitor of aspartate proteases, 1,2-epoxy-3-(p-nitrophenoxy)propane, completely blocked toxin B function on cultured cells and was used to identify its catalytically active protease site. To our knowledge this is the first report on a bacterial toxin that useseukaryotic signals for induced autoproteolysis to deliver its toxic domaininto the cytosol of target cells. On the basis of our data, we present an integrated model for the uptake and inositolphosphate-induced activation oftoxin B.
    Vir: Nature : the international weekly journal of science. - ISSN 0028-0836 (Let. 446, št. 7134, 2007, str. 415-419)
    Vrsta gradiva - članek, sestavni del
    Leto - 2007
    Jezik - angleški
    COBISS.SI-ID - 58958849

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