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From Proteopedia
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Anthrax edema factor
Introduction
The anthrax edema factor is an 89 kDa exotoxin produced by Bacillus anthracis, the bacterium that causes anthrax. It is an adenylate cyclase [ATP pyrophospate-lyase (cyclizing)]. Its enzyme classification number is EC 4.6.1.1. The edema factor increases intracellular cyclic AMP (cAMP) concentration in eukaryotic cells. In fact adenylyl cyclases catalyze the conversion of adenosine triphosphate (ATP) into cAMP and pyrophosphate. The edema factor is produced in an inactive form and calmodulin-activated. Bacillus anthracis also secretes other proteins, in particular the protective antigen (83 kDa) and the lethal factor (90 kDa). Edema factor, protective antigen and lethal factor can also be called factor I, II and III respectively.
The edema factor is delivered into host cells thanks to the protective antigen. When it is in the cell, the edema factor is activated by calmodulin and its enzymatic activity leads to a dramatic elevation of the cAMP range. Cyclic AMP is a second messenger that plays key roles in the signal transduction pathways and thus regulates diverse cellular responses. It binds to three families of signal transducers: cAMP-dependent protein kinases, cyclic nucleotide gated channels, and the guanine nucleotide exchange factor for Ras GTPase homologs Rap1 and Rap2.
Associated disease
Different forms of disease
Anthrax develops when the organism enters in contact with spores of Bacillus anthracis. Syptoms are depending on the contamination mode. The cutaneous contamination results from a contact of spores with an injury. It leads to an ulcer and to the formation of vesicles. In 80 % of the cases the wound heals without complications. However, sometimes an oedema can develop itsel and grow. In that case, anthrax can lead to the death of the patient.
A gastrointestinal contamination can result from the consumption of contaminated meat. This form of anthrax leads to ulcers, nauseas, diarrhoea and blood poisonning. It can also be lethal if it is not rapidly treated.
Finally, anthrax spores can cause a pulmonary infection by inhalation. The symptoms developed are similar to those of influenza and they evolve into breathing difficulties and hypotension. Blood poisonning and meningitis can also occur. Because of the severe symptoms, the pulmonary infection remains highly lethal. The mortality is caused by the combined effects of bacterial toxins (toxaemia) and baterial growth (becteremia).
Action of the toxin
The secreted proteins can produce two toxic actions. The protective antigen associated with the lethal factor forms the lehtal toxin wile associated with the edema factor it forms the edema toxin. The lethal toxin is involved in the bacterial virulence. The edema toxin plays a key role in anthrax pathogenesis by modulating functions necessary for immunity.
Injection of the lethal toxin causes death of rats, whereas the edema toxin causes oedema in the skin of guinea pigs.
Since the edema factor secreted by Bacillus anthracis leads to a massive cAMP formation, it affects intracellular signalling pathways. This factor may also play a key role in anthrax pathogenesis by disrupting the host cell's defence against bacterial infection. The toxin has effects on macrophages, dendritic cells, neutrophils, endothelial cells and on the antigen presentation of T cells. Fot instance, it inhibits the phagocytic activity of neutrophils and alters cytokine production of monocytes.
