16.3
Inhalation Anthrax
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Q1: How do Bacillus anthracis spores enter the body in inhalation anthrax?
In inhalation anthrax, aerosolized Bacillus anthracis spores are inhaled and deposited directly in the alveolar spaces of the lungs. This represents the most severe form of anthrax infection. The spores then encounter alveolar macrophages, which internalize them through phagocytosis and transport them to regional lymph nodes where germination occurs.
Q2: What role do alveolar macrophages play in inhalation anthrax infection?
Alveolar macrophages phagocytose Bacillus anthracis spores and transport them to lymph nodes. Once in the lymph nodes, spores germinate into vegetative bacteria. The bacteria then kill the macrophages as they exit, allowing the infection to spread systemically and establish a foothold in the host.
Q3: What are the two plasmids that encode virulence factors in Bacillus anthracis?
Bacillus anthracis carries pXO2 and pXO1 plasmids. pXO2 encodes a poly-D-glutamic acid capsule that inhibits phagocytosis, protecting bacteria from immune destruction. pXO1 encodes the anthrax exotoxin composed of three proteins: Protective Antigen, Edema Factor, and Lethal Factor, which together cause severe tissue damage and systemic effects.
Q4: How does Protective Antigen facilitate toxin entry into host cells?
Protective Antigen binds to specific host cell receptors and mediates endocytosis of Edema Factor and Lethal Factor into the cell. Inside the acidified endosome, Protective Antigen oligomerizes into a pore that translocates these toxins into the host cytoplasm, where they disrupt cellular functions and trigger cell death.
Q5: What cellular damage do Edema Factor and Lethal Factor cause in inhalation anthrax?
Edema Factor is a calmodulin-dependent adenylate cyclase that increases intracellular cyclic AMP, disrupting ion balance and causing tissue edema. Lethal Factor is a zinc-dependent metalloprotease that cleaves mitogen-activated protein kinase kinases, interrupting signal transduction and triggering apoptosis of immune and endothelial cells.
Q6: How does inhalation anthrax progress to systemic shock and organ failure?
As infection advances, vegetative bacteria proliferate and release Edema Factor and Lethal Factor into the bloodstream. These toxins cause widespread vascular leakage, impair immune response, and trigger systemic intoxication. This cascade leads to vascular collapse, systemic shock, and multiple organ failure if untreated, making inhalation anthrax highly lethal.
Q7: How does inhalation anthrax differ from other forms of anthrax infection?
Inhalation anthrax is the most severe form, with spores deposited directly in lung alveoli. Cutaneous anthrax results from skin contact and is generally less severe. Gastrointestinal anthrax follows ingestion of contaminated meat and affects the digestive tract, similar to bacterial gastroenteritis. Injection anthrax, a rare form from contaminated drugs, resembles cutaneous anthrax but spreads faster with deeper tissue damage.