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Mechanism Of Anthrax Toxins


Anthrax is an acute infectious disease caused by the spore-forming gram positive, aerobic bacterium Bacillus anthracis, whose pathogenesis is primarily the result of a tripartite toxin. This toxin is composed of three proteins: the Protective Antigen (PA), the Edema Factor (EF) and the Lethal Factor (LF). These proteins work together to enter a cell and disrupt the signaling pathways. Secreted from the bacteria as nontoxic monomers, these proteins assemble on the surface of Anthrax Toxin Receptor (ATR)-bearing eukaryotic cells to form toxic noncovalent complexes. The process starts when the 83 kDa PA (PA83) monomers bind to the ATR Receptor. Once bound, a 20 kDa N-terminal fragment (PA20) is cleaved off of PA83,leaving behind the remaining 63 kDa portion (PA63). PA63 rapidly oligomerizes to form a heptamer pre-pore,which then associates with up to three molecules of EF and/or LF.

The cell then endocytoses the complex and carries it to an acidic compartment, where the low pH causes a conformational change in the PA63 pre-pore that forms a cation-specific channel and allows the EF and LF to enter into the cytosol. Once in the cytosol, the EF and LF then carry out their respective damage-inducing processes, ultimately causing Apoptosis. Anthrax is a disease that has plagued man and his livestock for centuries, causing it to be one of the most well-studied and understood diseases. This animation provides an overview of the mechanism of Anthrax toxin in case of pulmonary infection, the most fatal form of infection causing Anthrax.

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