"Unlike most types of bacteria, Bacillus anthracis has the ability to produce large amounts of a toxin that can kill the patient even after antibiotics have destroyed the bacteria," explains the study's senior author Lewis Cantley, Ph.D., Chief of the Division of Signal Transduction at BIDMC and Professor of Systems Biology at HMS. "This toxin is released within days of the initial infection, and is impervious to antibiotics." Because the initial symptoms of the disease fever, cough and chest pain mimic colds and flu, early diagnosis is extremely difficult; as a result, some 90 percent of all cases of inhalational anthrax prove fatal.
"Toxins act in two ways," adds BIDMC scientist and first author Benjamin Turk, Ph.D. "First, they cripple the cells that fight bacterial infection, thereby enabling the spread of bacteria early in the disease. Later in the process," he adds, "they contribute to the death of macrophage cells, leading to the shutdown of the body's immune system." In fact, autopsies of patients who have died from inhalational anthrax reveal that the high doses of antibiotics have killed the bacteria, indicating that the patients have died from the toxins rather than a persistent infection.
Using a "mixture-based peptide library" technique developed by Turk, the researchers analyzed trillions of peptides to determine an optimal peptide substrate for lethal factor, the active agent in the