Anthrax toxin

Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes. Anthrax is a disease caused by Bacillus anthracis, a spore-forming, Gram positive, rod-shaped bacterium (Fig. 1). The lethality of the disease is caused by the bacterium's two principal virulence factors: (i) the polyglutamic acid capsule, which is anti-phagocytic, and (ii) the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF). Anthrax toxin is an A-B toxin. Each individual anthrax toxin protein is nontoxic. Toxic symptoms are not observed when these proteins are injected individually into laboratory animals. The co-injection of PA and EF causes edema, and the co-injection of PA and LF is lethal. The former combination is called edema toxin, and the latter combination is called lethal toxin. Thus the manifestation of physiological symptoms requires PA, in either case.