Bacillus anthracis is a rod-shaped, Gram-positive bacterium that causes anthrax, a severe disease in livestock and humans. This organism is considered an obligate pathogen within the Bacillus genus. Its status as a biological weapon concern highlights the resilient spore form. The bacterium’s ability to cause disease is linked to specific virulence factors.
The Virulence Factors: Spores and Toxins
The effects of anthrax infection are attributable to two primary virulence factors: the formation of a protective capsule and the secretion of a potent tripartite toxin. The genes for these factors are carried on two plasmids, designated pXO1 and pXO2. Plasmid pXO2 encodes the poly-D-gamma-glutamic acid capsule, which acts as an antiphagocytic shield, allowing the bacteria to evade the host’s immune cells.
The pXO1 plasmid carries the genes for the three protein components that make up the anthrax toxin: Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF). These components are non-toxic individually but combine in binary pairs to form two active toxins: Lethal Toxin (LT) and Edema Toxin (ET).
Protective Antigen (PA) is the shared binding component, attaching to host cell receptors and forming a pore that mediates the entry of the other two factors. Lethal Toxin (LT) forms when PA combines with LF, a zinc-dependent protease. Once inside the cell, LF cleaves and inactivates specific signaling proteins, ultimately leading to cell death and tissue necrosis.
Edema Toxin, the combination of PA and EF, disrupts the cell’s water balance. Edema Factor is a calmodulin-dependent adenylate cyclase, which dramatically increases the concentration of cyclic AMP (cAMP) within the host cell. This excessive buildup of cAMP impairs normal cell function and leads to the massive fluid accumulation and swelling characteristic of the disease.
The infection cycle begins with the spore, the dormant, highly resilient form of B. anthracis that can survive in soil for decades. Upon entering a host through a break in the skin, inhalation, or ingestion, the spores sense the nutrient-rich environment and germinate into active, multiplying vegetative cells. These vegetative cells then produce the capsule and the toxins, enabling rapid systemic infection.
Clinical Manifestations of Anthrax Infection
Anthrax infection in humans presents in three main clinical forms, each dictated by the route of spore entry. Cutaneous anthrax is the most common form. It occurs when spores enter a cut or abrasion on the skin, typically presenting as an itchy, raised bump that develops into a painless ulcer with a black, necrotic center called an eschar. With appropriate treatment, the mortality rate for cutaneous anthrax is very low, close to one percent.
Inhalation anthrax is the most dangerous form, contracted by breathing in aerosolized spores that travel to the lymph nodes in the chest. Initial symptoms are non-specific and flu-like, making early diagnosis difficult. This is followed by severe respiratory distress and shock. Even with aggressive medical intervention, the mortality rate for inhalation anthrax remains high, around 45 percent.
Gastrointestinal anthrax is rare and results from consuming undercooked meat contaminated with spores from an infected animal. This form can affect the upper gastrointestinal tract, causing severe sore throat and neck swelling, or the lower tract, leading to abdominal pain and bloody diarrhea. Without treatment, gastrointestinal anthrax has a high mortality rate, often exceeding 50 percent. A fourth, less common form, injection anthrax, has also been identified in people who inject illicit drugs, presenting with deep soft-tissue infections.
Non-Pathogenic Strains and Vaccine Development
Strains that are considered non-virulent have been naturally or artificially ‘cured’ of one or both of the virulence-encoding plasmids, pXO1 and pXO2. For instance, the Sterne strain, widely used for livestock vaccination, is a toxigenic but non-encapsulated strain. It retains the pXO1 plasmid but lacks pXO2. The absence of the antiphagocytic capsule prevents the bacterium from causing full-blown disease, but the production of the toxin components is retained.
This non-pathogenic but toxigenic characteristic is leveraged for vaccine development. The goal of current anthrax vaccines is to generate a strong immune response against the Protective Antigen (PA) component of the toxin. The current human vaccine, Anthrax Vaccine Adsorbed (AVA or BioThrax), is an acellular vaccine made from the culture filtrate of an attenuated, non-encapsulated, toxigenic strain. The antibodies generated against PA are designed to neutralize the active toxins by blocking PA’s ability to bind to host cells.
Medical Response: Treatment and Prevention
Post-exposure prophylaxis (PEP) is administered to individuals exposed to B. anthracis spores who are not yet showing symptoms. PEP typically involves a 60-day course of antimicrobial drugs, such as Ciprofloxacin or Doxycycline, to prevent dormant spores from germinating and causing disease.
Active treatment for confirmed infection combines antimicrobial drugs with antitoxins. Antitoxin therapies, such as monoclonal antibodies, are used because antibiotics only kill the bacteria; they do not neutralize the toxins already circulating in the bloodstream. This combination therapy targets both the replicating organism and the life-threatening effects of the toxins.
Vaccination is a primary prevention measure, although it is typically reserved for high-risk groups, including certain laboratory personnel and military service members. The vaccine is administered in a multi-dose regimen to generate long-lasting immunity. In the event of a bioterrorism-related exposure, the combination of a 60-day course of antibiotics and the anthrax vaccine is recommended to maximize protection against the deadly inhalation form of the disease.