Anthrax exposed and killed

New antibiotic seeks and destroys bioterror agent.
22 August 2002

HELEN PEARSON

Antibiotic makes the anthrax bacterium's cell wall bud out, then disintegrate. source: Nature

A new drug could foil bioterrorists' attempts to engineer antibiotic-resistant anthrax. The drug could also make a quick hand-held detector for checking contaminated sites, say US scientists.

The anthrax used in last October's US mail attacks was treatable, but future strikes could be worse. "Any sophisticated terrorist could easily engineer strains to be resistant to antibiotics," says anthrax researcher Stephen Leppla of the National Institutes of Health in Bethesda, Maryland.

The new drug dissolves a vital component of the bacterium's cell wall¹. It would be virtually impossible to create strains that could withstand this, says Vincent Fischetti of Rockefeller University in New York.

The drug also detects anthrax spores, the tough forms of the bacteria used in bioweapons. Suspected spores are applied to a filter and treated to make them sprout. Burst open by the drug, bacterial innards can be detected in minutes using a fluorescent dye and a hand-held light detector.

"If you have a contaminated area you'd know whether to evacuate or treat people," says Fischetti. During last year's attacks, it took labs days to give buildings the all-clear.

A rapid detector would be "a huge advance", agrees Leppla. "It could give an answer in a half hour."

Virus strike

The Rockefeller team exploited a virus called a bacteriophage that invades and kills Baccillus anthracis. They extracted a protein called PlyG lysin, which normally bursts bacteria open after the virus has entered and reproduced inside.

PlyG lysin can kill 50 million bacteria in two minutes, they found, making it more potent than many antibiotics. And an injection of PlyG lysin saved three-quarters of mice given an infection that would otherwise kill them. A higher dose of enzyme should save the remainder, the team hope.

Such 'phage therapy' is routine in Russia - the concept is over 80 years old - but was ousted by antibiotics in the West. This is partly because bacteria rapidly evolve resistance to phage.

Not so for PlyG lysin: "So far we've never seen a resistant organism," says Fischetti. The group experimented with mutating bacterial DNA, which generates strains impervious to standard antibiotics.

The team plan to start clinical trials on animals within weeks. The drug could be ready to stockpile within three years, predicts Fischetti.

Despite the use of antibiotics, 5 of the 22 infections during last year's attacks were fatal. By the time anthrax is diagnosed, the bacteria have often released large amounts of toxin.

Many researchers are trying to find drugs to neutralize the toxin. Others are working on vaccines.

Nano-bullets

This week scientists also revealed a powder of magnesium oxide that can scour contaminated rooms of anthrax spores².

Before (top) and after: nanoparticles attack anthrax spores' tough coat. © P. Stoimenov

Unlike antibacterial gases and foams, which are messy, corrosive and ruin electrical equipment, the powder could be sprayed into rooms and swept or vacuumed up, says chemist Kenneth Klabunde of Kansas State University.

The chemical specks attract oppositely charged spores, Klabunde and his team found. The particles then cut open and chemically break down the spores' tough outer shell.

The team tested the powder by blowing spores into a stainless-steel room, then cleaning them up with a squirt of nanoparticles.

Both groups hope that their techniques can be used to treat other diseases. Fischetti's team have found a phage lysin that targets pneumonia-causing bacteria.

1. Schuch, R., Nelson, D. & Fischetti, V.A. A bacteriolytic agent that detects and kills Bacillus anthracis. Nature, 418, 884 - 889, (2002).
2. Stoimenov, P.K. et al. Metal Oxide Nanoparticles as Bactericidal Agents. Langmuir, 18, 6679 - 6696, (2002).