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Cross-Reactivity of Anthrax and C2 Toxin: Protective Antigen Promotes the Uptake of Botulinum C2I Toxin into Human Endothelial Cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-134791
  • Binary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the AB(7/8) type of toxins. The B subunits bind both host cell receptors and the enzymatic A polypeptides to trigger their internalization and translocation into the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase (C2I) and C2II binding subunits. Anthrax toxin is composed of adenylate cyclaseBinary toxins are among the most potent bacterial protein toxins performing a cooperative mode of translocation and exhibit fatal enzymatic activities in eukaryotic cells. Anthrax and C2 toxin are the most prominent examples for the AB(7/8) type of toxins. The B subunits bind both host cell receptors and the enzymatic A polypeptides to trigger their internalization and translocation into the host cell cytosol. C2 toxin is composed of an actin ADP-ribosyltransferase (C2I) and C2II binding subunits. Anthrax toxin is composed of adenylate cyclase (EF) and MAPKK protease (LF) enzymatic components associated to protective antigen (PA) binding subunit. The binding and translocation components anthrax protective antigen (PA(63)) and C2II of C2 toxin share a sequence homology of about 35%, suggesting that they might substitute for each other. Here we show by conducting in vitro measurements that PA(63) binds C2I and that C2II can bind both EF and LF. Anthrax edema factor (EF) and lethal factor (LF) have higher affinities to bind to channels formed by C2II than C2 toxin's C2I binds to anthrax protective antigen (PA(63)). Furthermore, we could demonstrate that PA in high concentration has the ability to transport the enzymatic moiety C2I into target cells, causing actin modification and cell rounding. In contrast, C2II does not show significant capacity to promote cell intoxication by EF and LF. Together, our data unveiled the remarkable flexibility of PA in promoting C2I heterologous polypeptide translocation into cells.show moreshow less

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Metadaten
Author: Kronhardt Angelika, Monica Rolando, Christoph Beitzinger, Caroline Stefani, Michael Leuber, Gilles Flatau, Michel R. Popoff, Roland Benz, Emmanuel Lemichez
URN:urn:nbn:de:bvb:20-opus-134791
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:German
Parent Title (German):PLoS ONE
Year of Completion:2011
Volume:6
Issue:8
Pagenumber:e23133
Source:PLoS ONE 6(8): e23133. doi:10.1371/journal.pone.0023133
DOI:https://doi.org/10.1371/journal.pone.0023133
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Clostridium-botulinum; Crystal-structure; Current noise-analysis; Edema factor; Escherichia-coli; Ion-channel; Lethal factor; Lipid bilayer-membranes; Matrix protein porin; Phenylalanine clamp
Release Date:2019/03/25
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung