Findings could lead to novel treatments against other bacterial infections

Boston, MAA study by Harvard Medical School researchers in the April 27 Science suggests a mutation in the anthrax toxin, which prevents poisoning, may lead to a double-pronged pharmaceutical that is equally effective as a vaccine and as a faster-acting and more broadly protective therapy than currently available.

Death from anthrax is due to the toxin produced by the bacteria. In its airborne form, just a teaspoonful of anthrax could wipe out hundreds of people. Though rarely a natural threat to humans, anthrax is especially dangerous as a potential weapon in terrorism and biological warfare.

Though a vaccine exists, most people have no vaccine-induced immunity to anthrax because the rarity of infection makes a mass vaccination program impractical. Yet current therapies demand that any unvaccinated person exposed to the bug receive antibiotic therapy before symptoms occur. Otherwise, the victim with systemic anthrax dies rapidly. The discovery by R. John Collier and colleagues may offer a better way to fight back before or after infection.

The researchers tested whether they could prevent infection using forms of the anthrax bacterium with a mutation in a toxin subunit dubbed "protective antigen." When protective-antigen mutants were injected together with a normally lethal mix of toxin, rats did not develop any symptoms of poisoning. The protective-antigen variants "totally protected the animals, whereas the control animals became moribund within 90 minutes," says Collier, the Maude and Lillian Presley Professor of Microbiology and Molecular Genetics at the Medical School. "Were most encouraged about the experiments in rats. The results are remarkable."

The protective-antigen mutants are good candidates for an anthrax therapy because the normal form of protective antigen in and of itself is already known to be safe in humans: it is the major component
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Contact: John Lacey
john_lacey@hms.harvard.edu
617-432-0441
Harvard Medical School
26-Apr-2001