Degrading a Defense: Bacteria use enzyme to escape trap

Like a cloak of invisibility, an enzyme released by strep A bacteria lets them slip away from the body’s staunchest defenders, a new study shows. The discovery could lead to a new weapon against virulent diseases.

White blood cells called neutrophils have a two-pronged defense against bacteria: They can swallow and destroy them or they can release neutrophil extracellular traps (NETs). The fibrous NETs are made up of DNA and toxic compounds that can catch and kill pathogenic microbes.

But some bacteria nimbly evade NETs, says Victor Nizet of the University of California, San Diego. One possible explanation has been that those bacteria produce an enzyme that degrades the traps.

Disease-producing bacteria seem to make more of an enzyme called DNase than benign microbes do, Nizet says. “There’s been speculation for a long time that DNases could be virulent,” he says.

Group A streptococcus bacteria can cause diseases ranging from throat infections to scarlet fever to flesh-eating disease, and they’re highly resistant to the neutrophils’ traps.

To test whether it is DNase that helps strep A bacteria escape NETs, the researchers created a mutant strain of the bacteria that lacked the gene that encodes for DNase. Without the gene, the bacteria didn’t degrade the NETs and were quickly killed by cultured neutrophils.

The team also inserted the DNase gene into benign bacteria that normally lack the enzyme. In laboratory tests, the altered microbes evaded the NETs with ease. “This showed that manipulating this one bacterial-virulence factor has a big effect on the disease-causing potential of bacteria,” Nizet says.

In the same study, the researchers injected a chemical DNase inhibitor into one hind leg of each of four mice infected with flesh-eating strep disease and injected a placebo into the other hind leg. In placebo-treated limbs, where the bacteria were “running rampant,” Nizet says, there were no fibrous NETs. In all the inhibitor-treated limbs, however, the scientists saw abundant NETs. In lesions there, no bacteria remained and no ulcers developed, says Nizet. He and his team report the results in the Feb. 21 Current Biology.

The paper “clearly shows” that strep A makes an enzyme that can destroy NETs, says microbiologist Arturo Zychlinsky of the Max Planck Institute for Infection Biology in Berlin. “It’s extremely interesting.” In the Feb. 21 Current Biology, Zychlinsky describes a similar enzyme secreted by pneumococcus bacteria.

Nizet says that his team’s discovery could guide a new approach to fighting disease, although researchers will first need to find ways to target only pathogenic DNases. Rather than killing the bacteria with antibiotics, and thereby encouraging them to evolve resistance, he says, “we’re basically allowing the immune system to do its job.”