Pore-forming activity of clostridial binary toxins

Abstract

Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity

“…ASMase subsequently induces endocytosis as well as mediating the uptake of pathogens into cells. C2IIa forms ion-permeable channels in planar phospholipid bilayer membranes (4). In the present study, C2IIa was easily internalized in the presence of Ca 2ϩ but not in the absence of Ca 2ϩ .…”

“…C2 toxin is an enterotoxin correlated with serious animal enteric diseases (4). In the present study, ASMase inhibitors blocked the internalization of C2 toxin; therefore, the blocking of ASMase may provide new avenues for drug treatment.…”

“…The two components represent separate proteins, which are devoid of toxic activity when injected alone (4). Only the combination of the two components shows a cytopathic effect on cells.…”

“…C lostridium botulinum produces a binary toxin, C2, which consists of two nonlinked proteins called C2I (active enzymatic component) and C2II (binding component) (1)(2)(3)(4). The two components represent separate proteins, which are devoid of toxic activity when injected alone (4).…”

“…C2 toxin is a member of the binary actin-ADP-ribosylating toxin family. Members of this toxin family include Clostridium perfringens iota-toxin, Clostridium spiroforme iota-like toxin, Clostridium difficile ADP-ribosyltransferase, and vegetative insecticidal protein from Bacillus cereus (1)(2)(3)(4).…”