Quantifying an Anthrax LF Inhibitor in Human Plasma by HPLC-MS-MS

Bacillus anthracis, the etiological agent of anthrax, is a Gram-positive, rod-shaped bacterium that forms spores that are highly resistant to heat, ultraviolet light, radiation, pressure, and chemical agents. The durability of these spores make this bacterium a potential bioweapon (1).

Immediate treatment of anthrax infection with antibiotics is very effective. There is a limited period of time in which an infected patient, who might only exhibit mild flu-like symptoms, can be saved with antibiotic therapy. Toxins released by anthrax cause a patient to succumb to infection well after antibiotics have killed the anthrax bacteria. The major virulence factor of anthrax infection is Lethal Factor (LF), a zinc-dependent metalloprotease toxin. LF disrupts MAP kinase signaling pathways, resulting in cytotoxicity. MAP kinase signaling pathways regulate proinflammatory cytokines. Overproduction of these cytokines is associated with septic shock, respiratory distress, and multiorgan failure leading to death (1–6). Injection of the lethal toxin alone into mammals results in death. Research has demonstrated that inhibiting the activity of LF can reduce tissue damage associated with anthrax infection (7).