Anthrax is a severe infectious disease caused by the bacterium Bacillus anthracis. The organism itself does not cause illness directly; instead, it produces potent protein molecules that function as toxins inside the body. The resulting symptoms of anthrax, such as tissue damage and immune system disruption, are entirely dependent on the actions of these complex, multi-part toxins. Understanding anthrax requires examining the structure of the bacterium and the molecular machinery it secretes to cause damage.
The Core Component: Bacillus anthracis
The causative agent of anthrax is the Gram-positive bacterium Bacillus anthracis, a rod-shaped microorganism. A defining feature is the outer poly-D-γ-glutamic acid capsule, which is a significant factor in virulence. This gelatinous coating protects the multiplying bacteria from being engulfed and destroyed by the host’s immune cells, such as phagocytes.
The primary infectious form is not the active bacterium but a dormant structure known as an endospore. Endospores are highly resilient, protective shells formed when environmental conditions become unfavorable for growth. This structure allows the bacteria to persist in soil for decades, resisting extreme temperatures, dehydration, and chemical disinfectants.
When these spores enter a hospitable environment, such as a host body, they rapidly germinate into active, replicating vegetative cells. These growing cells multiply and secrete the complex proteins that make up the anthrax toxin. The organism’s full virulence depends on two large, circular pieces of extrachromosomal DNA called plasmids, which encode the toxin components and the capsule.
The Weapon System: Anthrax Toxin Composition
The toxic components of anthrax are not a single molecule but a set of three distinct proteins that must combine to exert damaging effects. These three proteins—Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF)—are secreted individually by the bacteria and are non-toxic on their own.
Protective Antigen (PA) is the largest component and acts as the cell-binding and transport unit for LF and EF. PA must first bind to a receptor on the host cell surface to initiate intoxication. Lethal Factor (LF) and Edema Factor (EF) are the two catalytic components, functioning as enzymes that carry out destructive actions inside the host cell.
The three proteins combine in specific pairings to form the two active toxins that produce disease symptoms. Protective Antigen paired with Lethal Factor forms the Lethal Toxin (LT), which causes tissue destruction and cell death. Protective Antigen paired with Edema Factor creates the Edema Toxin (ET), which is responsible for the fluid accumulation and swelling (edema).
Mechanism of Cellular Entry and Action
The process of intoxication begins when the 83 kilodalton form of Protective Antigen (PA83) binds to specific anthrax toxin receptors on the host cell surface. Once bound, host cell proteases—enzymes that cleave proteins—cut off a 20 kilodalton fragment from PA83, leaving the active 63 kilodalton fragment (PA63). This cleavage activates the toxin delivery system.
The remaining PA63 fragment spontaneously assembles with six other PA63 molecules to form a ring-shaped structure called a heptamer prepore. This seven-sided ring can bind up to three molecules of Lethal Factor or Edema Factor. The entire complex (the PA heptamer bound to LF and/or EF) is then internalized by the host cell through endocytosis.
The complex is contained within an internal bubble called an endosome, where the environment becomes acidic. This low pH triggers a conformational shift in the PA63 heptamer, causing it to insert into the endosome membrane and form a pore. Through this channel, the LF and EF molecules are threaded into the host cell’s main compartment, the cytosol, where they execute their toxic effects.
Once delivered into the cytosol, Lethal Factor (LF) and Edema Factor (EF) target specific cellular pathways. LF is a zinc-dependent protease that cleaves and inactivates key signaling molecules, specifically members of the Mitogen-Activated Protein Kinase Kinase (MAPKK) family. This disruption of communication pathways often leads to cell death, particularly in immune cells like macrophages. EF is an adenylate cyclase enzyme that uses calcium and a host protein called calmodulin to increase the production of cyclic AMP (cAMP) inside the cell. The excessive buildup of cAMP disrupts the balance of water and ions, leading to fluid leakage and swelling characteristic of edema.