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Lethal Factor

Lethal Factor (LF), a protein comprised of 776 amino acids, is the dominant exotoxin produced by B. anthracis and, when combined with protective antigen, is the major cause of death of infected animals. Examination of the lethal factor amino acid sequence shows that it contains a purported zinc binding motif HEXXH which supports evidence that it functions as a metalloprotease (10). Once it has gained entry into the macrophage, this metalloprotease targets Mitogen Activated Protein Kinase Kinases(MAPKK), which are involved in intracellular signaling pathways, where it cleaves ~30 amino acids from the N terminus of the protein, which inactivates it and prevents it from activating p38 MAPKs (11). Normal P-38 activity is required for expression of kB genes which prevent apoptosis of activated macrophages. Since this activity is blocked in the infected individual, activated macrophages are sent to their death and are prevented from secreting cytokines necessary to activate the cellular and humoral arm of the immune system, and the bacteria are able to multiply without restraint until the untreated patient becomes septic.

Ribbon Model of Lethal Factor (1)