Expression of Bacillus Anthracis Protective Antigen in Salmonella Typhimurium

Abstract

Anthrax is an infectious disease known since antiquity. It is nearly universal in its geographic distribution and, although primarily a disease of herbivores, it can affect many species and it has important zoonotic implications. Anthrax is caused by Bacillus anthracis, a gram positive, non-motile, aerobic and facultatively anaerobic spore-forming organism. Two main virulence factors have been identified, one is a three-component protein exotoxin, termed the anthrax toxin, and the other a poly-D-glutamic acid capsule. These factors are carried on plasmids termed pXO1 and pXO2 respectively. Anthrax toxin is composed of three components, Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF). PA is secreted as a 83 KDa protein which is cleaved in the serum, or on the cell surface, to release a 20 KDa N-terminal fragment. The remaining 63 KDa fragment binds to a specific cell surface receptor and can then bind either EF or LF. The combination of PA and LF is referred to as Lethal Toxin, and PA and EF is called Edema Toxin. This is illustrated in Figure 1. The toxins therefore fit the A/B model with the 63KDa C-terminal fragment of trypsin cleaved PA being equivalent to the receptor-binding region (B moiety) which can then bind and internalize either EF or LF (alternative a moieties). Edema Toxin causes oedema when injected intradermally in animals and EF is an adenylate cyclase. When injected intravenously in susceptible animals Lethal Toxin causes rapid death but it’s mechanism of action is unknown although it is assumed to have an enzymatic action within the cytosol.