EGA protects mammalian cells from Clostridium difficile CDT, Clostridium perfringens iota toxin, and Clostridium botulinum C2 toxin

Abstract: The pathogenic bacteria Clostridium difficile, Clostridium perfringens and Clostridium botulinum produce the binary actin ADP-ribosylating toxins CDT, iota and C2, respectively. These toxins are composed of a transport component (B) and a separate enzyme component (A). When both components assemble on the surface of mammalian target cells, the B components mediate the entry of the A components via endosomes into the cytosol. Here, the A components ADP-ribosylate G-actin, resulting in depolymerization of F-actin, cell-rounding and eventually death. In the present study, we demonstrate that 4-bromobenzaldehyde N-(2,6-dimethylphenyl)semicarbazone (EGA), a compound that protects cells from multiple toxins and viruses, also protects different mammalian epithelial cells from all three binary actin ADP-ribosylating toxins. In contrast, EGA did not inhibit the intoxication of cells with Clostridium difficile toxins A and B, indicating a possible different entry route for this toxin. EGA does not affect either the binding of the C2 toxin to the cells surface or the enzyme activity of the A components of CDT, iota and C2, suggesting that this compound interferes with cellular uptake of the toxins. Moreover, for C2 toxin, we demonstrated that EGA inhibits the pH-dependent transport of the A component across cell membranes. EGA is not cytotoxic, and therefore, we propose it as a lead compound for the development of novel pharmacological inhibitors against clostridial binary actin ADP-ribosylating toxins

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Toxins. 8, 4 (2016), 101, DOI 10.3390/toxins8040101, issn: 2072-6651 ; IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs

Klassifikation und Themen

• Schlagwort: Toxikologie ; Vergiftung

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2016
• Urheber: Schnell, Leonie ; Mittler, Ann-Katrin ; Sadi, Mirko ; Schwan, Carsten ; Aktories, Klaus
• Beteiligte Personen und Organisationen: Albert-Ludwigs-Universität Freiburg. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Albert-Ludwigs-Universität Freiburg

Weitere Informationen

• DOI: 10.3390/toxins8040101
• URN: urn:nbn:de:bsz:25-freidok-132266
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:48 MEZ