Inhalation Anthrax

Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.

Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or intestines and causes symptoms like nausea, vomiting, abdominal pain, and severe diarrhea. Inhalational anthrax, the most severe form, begins when aerosolized spores are inhaled and deposited in the alveolar spaces of the lungs. Alveolar macrophages then internalize the spores through phagocytosis and transport them to regional lymph nodes. There, the spores germinate into vegetative bacilli—likely after macrophage lysis or in response to a nutrient-rich environment. Injection anthrax is a rare form seen in people who inject contaminated drugs. It resembles cutaneous anthrax but spreads faster, is harder to diagnose, and often involves deeper tissue damage.

Two plasmids, pXO1 and pXO2, mediate the pathogenesis of B. anthracis. The pXO2 plasmid encodes a poly-D-glutamic acid capsule that protects the bacteria from phagocytic destruction by host immune cells. This antiphagocytic capsule is a critical virulence factor, enabling the bacteria to evade host defenses and disseminate within the host.

The pXO1 plasmid encodes a tripartite exotoxin composed of Protective Antigen (PA), Edema Factor (EF), and Lethal Factor (LF). PA initiates toxin entry by binding to specific host cell receptors and mediating endocytosis of EF and LF. Within the acidified endosome, PA oligomerizes into a heptameric or octameric pore on the endosomal membrane to translocate EF and LF into the cytoplasm.

Edema Factor is a calmodulin-dependent adenylate cyclase that increases intracellular cyclic AMP (cAMP) levels, disrupting cellular ion balance and leading to fluid accumulation and tissue edema. Lethal Factor is a zinc-dependent metalloprotease that cleaves mitogen-activated protein kinase kinases (MAPKKs), interrupting key signal transduction pathways and resulting in apoptosis of immune and endothelial cells.

As the infection progresses, vegetative bacilli proliferate and release EF and LF into the bloodstream, contributing to systemic intoxication and tissue damage. This leads to widespread vascular leakage, impaired immune response, and eventually, systemic shock and multi-organ failure—underscoring the lethality of inhalational anthrax if untreated.

Due to its high lethality and ease of aerosolization, inhalational anthrax is a major concern in bioterrorism scenarios.