Anthrax Stopper: Viral enzyme detects, kills bacterium

Last fall, envelopes full of anthrax-causing spores killed 5 people, sickened about a dozen, and struck fear in millions. Researchers funded by the U.S. military have now developed an innovative way to detect and kill Bacillus anthracis, the bacterium that causes anthrax. Seeking help from nature, the researchers are using an enzyme produced by a bacteriophage, a virus that preys upon bacteria.

ANTHRAX ATTACK. A viral enzyme chews holes in the cell wall of Bacillus anthracis, allowing the anthrax bacterium’s contents to bubble out (arrows), which ultimately kills the germ. Rockefeller Univ.

The enzyme, called lysin, prevented the death of most mice that the researchers had infected with a bacterial relative of B. anthracis, Raymond Schuch of Rockefeller University in New York and his colleagues there report in the Aug. 22 Nature. The investigators also used the enzyme to create a prototype handheld instrument that quickly detects the anthrax bacterium, even in its spore form.

“This is a very clever exploitation” of lysin, says biowarfare researcher Stephen Morse of Columbia University.

Bacteriophages, or phages, infect bacteria in order to reproduce inside. Once they do, phages use lysin to break apart their host’s cell walls so the new phages can infect other bacteria. “They cause the [bacterium] to explode,” says study coauthor Vincent A. Fischetti.

Discovered nearly a century ago, bacteriophages have long attracted the interest of physicians seeking to control bacterial infections. Antibiotics stole the spotlight from phage therapy for many decades, but there’s renewed interest in the strategy, given the rise of antibiotic-resistant bacteria (SN: 6/1/96, p. 350; 6/3/00, p. 358: Viruses that slay bacteria draw new interest).

Over the past few years, Fischetti and his colleagues have exploited the bacteria-killing talent of phages in a different way. They’ve shown that lysin itself represents a new way to destroy bacteria. For example, they’ve successfully used lysin to treat animals infected with bacteria that cause strep throat and pneumonia in people (SN: 6/10/00, p. 376).

Fischetti’s group recently turned its attention to potential biowarfare agents, starting with the anthrax bacterium. While conventional antibiotics can treat many strains of B. anthracis, there’s concern that resistant strains could evolve or be created, says Fischetti.

He and his colleagues began working with a phage that infects the anthrax bacterium almost exclusively and identified the gene encoding its lysin. In test-tube experiments, the enzyme destroyed strains of B. anthracis collected from around the world but left most other bacteria unscathed.

Next, the scientists tested the enzyme on mice infected with a strain of Bacillus cereus closely related to the anthrax bacterium. This strain serves as an initial testing ground for anthrax therapies because B. anthracis is so dangerous to work with.

The B. cereus strain typically kills infected mice, but treatment with lysin saved up to 76 percent of infected animals, Fischetti’s team reports.

The researchers now plan to test the enzyme against B. anthracis, first in rodents and then in a nonhuman primate. If those experiments prove successful, physicians would then assess the safety of the viral protein in human volunteers. If lysin passes muster, the U.S. and other governments could then consider stockpiling the enzyme for any future anthrax attack.

Fischetti’s group also built a B. anthracis detector. The investigators mixed lysin with chemicals that emit a flash of light when exposed to a substance released by dead bacteria. They also added an agent that induces B. anthracis spores to germinate, making them susceptible to lysin. Finally, they engineered a handheld light meter to monitor this broth and found it could detect a signal produced by as few as 100 spores within an hour of adding them to the broth.

“It’s an innovative and promising strategy,” says Morse.

From the Nature Index

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