New insights into the mode of action of the actin ADP-ribosylating virulence factors Salmonella enterica SpvB and Clostridium botulinum C2 toxin.
The C2 toxin from Clostridium botulinum represents the prototype of the family of binary actin-ADP-ribosylating toxins. These toxins covalently transfer ADP-ribose from nicotinamide adenine dinucleotide (NAD(+)) onto arginine-177 of actin in the cytosol of eukaryotic cells resulting in depolymerization of actin filaments and cell rounding. The C2 toxin consists of two non-linked proteins, the enzyme component C2I and the binding and translocation component C2II, which delivers C2I into host cells. The ADP-ribosyltransferase SpvB from Salmonella enterica also modifies actin, but is delivered into the host cell cytosol from intracellular growing Salmonella, most likely via type-III-secretion. We characterized the mode of action of SpvB in comparison to C2 toxin in vitro and in intact cells. We identified arginine-177 as the target for SpvB-catalyzed mono-ADP-ribosylation of actin. To compare the cellular responses following modification of actin by SpvB or by the binary toxins without the influence of other Salmonella virulence factors, we constructed a cell-permeable fusion toxin to deliver the catalytic domain of SpvB (C/SpvB) into the cytosol of target cells. This review summarizes recent findings of research on the actin ADP-ribosylating toxins regarding their cellular uptake, molecular mode of action and the cellular consequences following ADP-ribosylation of actin.
Institut für Pharmakologie und Toxikologie, Universitätsklinikum Ulm, Germany. holger.barth@uni-ulm.de
Holger
H
Barth
Klaus
K
Aktories
D036002:ADP Ribose Transferases / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism*; D003014:Clostridium botulinum / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D019779:Salmonella enterica / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*
D000199:Actins; D037521:Virulence Factors; D036002:ADP Ribose Transferases; C415223:spvB protein, Salmonella enterica virulence plasmid; D001905:Botulinum Toxins; C096324:botulinum toxin type C