Anthrax Resistance Found in Some Mice

Bijal P. Trivedi
For National Geographic News
October 2, 2001
Some mice may be better prepared for anthrax attacks than others, a new
study reveals.

Researchers have discovered a gene variant that renders some mice strains resistant to a deadly toxin produced by the anthrax bacteria. The findings may eventually lead to new treatments and vaccines for the disease in humans.

Anthrax is an acute infectious disease. The anthrax bacterium, which causes the disease, is common—often found in cattle, sheep, goats, camels, antelopes, and other herbivores—and has received considerable attention because of its potential use as a bioweapon. Spores of the bacterium can be produced, stored, and dispersed during a biological attack.

After surveying the Kif1C gene in 20 strains of mice the researchers identified four versions—two that confer resistance to the anthrax toxin and two that seem to amplify its deadly effects. The work is published in the October issue of Current Biology.

The Kif1C gene produces a "motor protein" that shuttles cargo [proteins] along highways in the cell, says William Dietrich, of Harvard Medical School in Boston, Massachusetts, who led the research. Kif1C delivers proteins that have been manufactured and sorted to their destination in the cell.

The minute genetic differences seen between the protective and non-protective forms of Kif1C do not seem to affect its normal role in transporting proteins, yet "they are the difference between life and death," says Dietrich.

Anthrax kills by first obliterating the immune system of the host. The bacteria produce a toxin that is mistakenly imported by white blood cells, called macrophages, which are vital for destroying bacterial intruders. Once the toxin has entered the macrophage it triggers the production of highly reactive chemicals that cause the cell to burst and die. With low numbers of macrophages, anthrax can multiply unchallenged.

Macrophages containing the protective Kif1C are not susceptible to the toxin.

Dietrich and his colleagues speculate that the protective variant of Kif1C may transport the deadly toxin to a region of the cell where it can be destroyed. Another possibility, suggests Dietrich, is the protective Kif1C cannot carry the cargo that the toxin needs to trigger the deadly chemical reactions.

Although the human and mouse Kif1C genes differ in many regions, Dietrich suspects that similar genetic variations may exist. "I would like to see whether there are natural variants of the human Kif1C that protect against the anthrax toxin," he says. While conducting a survey of human Kif1C genes would be fairly routine work from a research point of view, Dietrich does not currently have a line-up of patients available for the survey.

Anthrax, a common bacterium—often found in cattle, sheep, goats, camels, antelopes, and other herbivores—has received considerable attention because of its potential use as a bioweapon.

Anthrax is particularly insidious because initial symptoms mimic the common cold or flu. Within days symptoms escalate to breathing problems, shock and then death. Early administration of antibiotics is an effective treatment in about 80 percent of cases. If left untreated the disease is fatal.

The most effective defense against anthrax is vaccination.The current version of the vaccine is difficult to produce and full treatment requires six shots followed by an annual booster.The vaccine is currently only available to military personnel and individuals working in high risk areas.

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