Anthrax genome unveiled

DNA sequence may help stop killer in its tracks.

1 May 2003

HELEN R. PILCHER

The anthrax bacterium is found naturally in farm animals. source: Nature

Researchers have decoded the genome of the bacterium that causes anthrax. The sequence may aid diagnosis, and highlight new targets for vaccine and drug development.

The sequence "is like a big Swiss army knife", says one of the team, Timothy Read of The Institute for Genomic Research in Rockville, Maryland. It contains more than 5,000 genes, with many different functions, suggesting that the bacteria can survive in a variety of environments.

Anthrax hit the headlines in 2001 when five people died after inhaling spores that had been sent through the post. This heightened concerns that anthrax could be used for bioterrorism. Around the world, the anthrax bacterium is found naturally in farm animals and other mammals.

Working out the sequence "is the beginning of understanding every facet of this organism", says Read. By unravelling the bug's basic biology, researchers may also be able to devise new screening protocols and decontamination strategies.

When nutrients are scarce, the anthrax bacterium forms small spores and can remain dormant for decades. The deadly, respiratory form of the disease arises when spores are inhaled into the fine airways of the lung. From there, the immune system can transport them to the lymph nodes, where they can germinate.

The active bacteria produce toxins that can enter the bloodstream and cause internal bleeding. Patients experience severe breathing difficulties, and more than 85% die.

Read's team deciphered the genetic code of Bacillus anthracis Ames, a virulent strain of the bacterium isolated from a dead Texan cow in 1981. The DNA readout features more than five million chemical 'bases' or letters¹.

A difference of just 11 letters separates the Ames strain from that which was used during the American postal attacks. They probably have a recent common ancestor, says Read.

The team identified a plethora of genes that enable the bacteria to cause disease. These include sequences for spore survival and activation. New drugs could be designed to target the proteins that these genes encode.

Read's group, and a second team lead by Natalia Ivanova of Integrated Genomics in Chicago, compared the genome of B. anthracis with those of related, less dangerous bacteria, including Bacillus cereus, which causes food poisoning in humans¹,².

Many of the genes are similar, the researchers found. But "what makes anthrax particularly nasty", says Colin Berry, who works on parasitic diseases at Cardiff University, UK, are the genes for virulence and toxicity that are housed on two extra DNA circles, separate from the bug's single chromosome.

B. anthracis and B. cereus also contain different forms of a gene that prompts bacteria to mutate. "This is switched on when the bug encounters a new environment, helping it to adapt," says Ivanova.

Compared to other environmental bacteria, the anthrax pathogen contains many more sequences that are involved in digesting proteins.

This hints that the microbe's ancestors may "have preyed on the dead or living bodies of insects and other animals", says Berry. Bacteria such as this may be "constantly ready and exquisitely able to adapt to and exploit any environmental or pathogenic niche that presents itself", he adds.

1. Read, T. D. et al. The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature, 423, 81 - 86, (2003).|Article|
2. Ivanova, N. et al. Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis. Nature, 423, 87 - 91, (2003). |Article|