A-B Type of Toxins: Mode of Transport and Interaction with Lipid Bilayers

Dear Colleagues, 

A-B types of toxins (so-called binary toxins) are potent virulence factors of certain Gram-positive bacteria. They consist of an enzymatic subunit A that is, in many cases, able to kill target cells by its enzymatic activity. The subunit B is secreted separately by the bacteria. It represents the binding/translocation subunit needed for the binding of toxins to target cells, and is responsible for the translocation of the enzymatic subunits into the cells via endosomal pathways. The most prominent example of this type of toxins is the tripartite anthrax toxin produced by Bacillus anthracis, which is listed by the World Health Organization (WHO) as a possible biological weapon. It consists of a binding protein, termed ‘protective antigen’, and two enzymatic subunits, the lethal factor and the edema factor, that are both able to kill target cells. Other prominent examples for A-B types of toxins are C2-toxin of Clostridium botulinum and Iota-toxin of Clostridium perfringens. Both toxins consist also of two distinct subunits that are secreted separately into the extracellular media: Component A is an actin-specific ADP-ribosyltransferase that is transported via component B into the target cells. After proteolytic activation, the binding components form ring-shaped heptamers. They form channels that mediate the transport of the enzymatic subunits of all A-B types of toxins into target cells via endosomal pathways. Reconstituted in lipid bilayers, the heptamers form cation-selective channels that can be blocked by interaction with the enzymatic subunits. They can also be blocked by positively charged heterocyclic molecules, such as chloroquine and related compounds. In vivo experiments also revealed that the same molecules inhibit intoxication by A-B types of toxins. The block of intoxication of target cells by compounds that bind to the heptamers is of considerable interest because of the possible use of A-B type of toxins as biological weapons.

Prof. Roland Benz
Guest Editor

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