Protective antigen is an 83‑kilodalton protein produced by Bacillus anthracis as one of the three components of the anthrax toxin. It binds to host cell receptors and allows the entry of lethal factor and edema factor into the cytosol.
Structure and function in anthrax toxin
The pathogenesis of anthrax involves a tripartite toxin composed of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is synthesised as an inactive precursor that recognizes host receptors such as tumor endothelium marker 8 and capillary morphogenesis protein 2. Host proteases cleave the 83‑kDa PA into a 63‑kDa fragment (PA63) that oligomerises on the cell surface to form a heptameric or octameric pre‑pore. Lethal factor is a zinc‑dependent metalloprotease, and edema factor is a calmodulin‑activated adenylate cyclase. These enzymatic components bind to the PA oligomer, which is then endocytosed. Acidification of the endosome triggers insertion of PA63 into the membrane, forming a transmembrane channel that translocates LF and EF into the cytosol. In macrophages, LF inactivates mitogen‑activated protein kinase kinases, causing cell death, while EF elevates cyclic AMP, leading to fluid accumulation. Neutralising antibodies against PA can block binding and pore formation, thereby preventing toxin entry.
Role in vaccination and therapeutics
Because PA is essential for the delivery of LF and EF and is highly immunogenic, it is the primary component of current anthrax vaccines. The licensed anthrax vaccine adsorbed (AVA) and anthrax vaccine precipitated (AVP) consist of filtrates containing PA adsorbed to aluminium salts to enhance the immune response. Vaccinated individuals produce anti‑PA antibodies that neutralise toxin activity. Recombinant PA is being evaluated in second‑generation vaccines and as a component of therapeutic monoclonal antibodies. Understanding the structure of PA has enabled the design of dominant‑negative mutants and small molecules that block pore formation, offering potential treatments for anthrax infection. Research on PA also informs the development of toxin‑based delivery systems for drugs and vaccines.
Protective antigen is therefore both a key virulence factor of B. anthracis and a target for protective immunity. Its unique role in toxin assembly makes it critical for understanding and counteracting anthrax disease.
Related Terms: Anthrax, Bacillus anthracis, Lethal Factor, Edema Factor, Toxin