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Toxins 2016, 8(4), 109; doi:10.3390/toxins8040109

Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B

Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
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Academic Editor: Holger Barth
Received: 21 March 2016 / Revised: 5 April 2016 / Accepted: 5 April 2016 / Published: 13 April 2016
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Abstract

Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the “Large clostridial glycosylating toxins.” These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB—together with Toxin A (TcdA)—is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn2+ > Co2+ > Mg2+ >> Ca2+, Cu2+, Zn2+. TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn2+ and 180 µM for Mg2+. TcsL and TcdB further require co-stimulation by monovalent K+ (not by Na+). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K+ and Mg2+ (rather than Mn2+) in mammalian target cells. View Full-Text
Keywords: glycosyltransferase; UDP-glucose hydrolysis; cytopathic effect; Rho; Ras; manganese; transepithelial resistance; small GTPases; Madin-Darby canine kidney (MDCK-C7) cells glycosyltransferase; UDP-glucose hydrolysis; cytopathic effect; Rho; Ras; manganese; transepithelial resistance; small GTPases; Madin-Darby canine kidney (MDCK-C7) cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Genth, H.; Schelle, I.; Just, I. Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B. Toxins 2016, 8, 109.

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