Annihilating Anthrax With Antibiotics

ClpXP mutation may be key to stopping tough bacterial infections.

(This article by Jenny Blair was published in the Spring 2018 issue of Endeavors.)

Anthrax has an Achilles’ heel — one that could help researchers create a new antibiotic to defeat the deadly bacteria as well as more common infections.

Shauna McGillivray, associate professor of biology at TCU, figured out how to render the bacteria harmless in mammals by subverting one of the key enzymes anthrax uses to create disease.

Photo of Shauna McGillivray

Biologist Shauna McGillivray at work in her TCU lab. McGillivray studies the deadly bacterial infection anthrax and believes it has an Achilles’ heel — one that could help researchers create a new antibiotic to defeat it as well as more common infections. (photo by Robert Hart)

That key is called ClpXP (clip-ex-P). It’s a protease, or an enzyme whose job is to take apart unwanted proteins. ClpXP is present in many bacteria, including anthrax and methicillin-resistant Staph aureus, or MRSA.

“The enzyme functions like a garbage disposal in the cell,” McGillivray said. “If you get rid of it, the cell doesn’t have a way to get rid of these proteins. … They can just kind of gunk up the cell.” A cell that can’t keep its own inner workings free of frayed, used-up protein machinery can stop functioning and die.

Several years ago, McGillivray found that by mutating one of the bacterial genes that encodes ClpXP, she could create a nonvirulent version of anthrax, one easily cleared up by the immune system in mice. (Her work at TCU involves a strain of the bacterium that is not harmful. But collaborators at the U.S. Army Medical Research Institute of Infectious Diseases who work with deadly wild-type anthrax found that a mutated ClpXP kneecaps that strain, too.)

Read more in Endeavors.