Anthrax Genome Sequenced

Researchers say the bacterium a close relative of soil bacterium

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By
HealthDay Reporter

WEDNESDAY, April 30, 2003 (HealthDayNews) -- Researchers have fully sequenced the genome of the bacterium that was implicated in the October 2001 anthrax attacks.

The research reveals that anthrax (Bacillus anthracis), which killed five people and injured 17 others in Florida, Washington, D.C., New York and Connecticut, is a close relative of a common bacterium found in soil.

Researchers believe the new information, detailed in two articles in the May 1 issue of Nature, will provide a foundation for future work on ways to combat anthrax infections.

"The completed genome and comparative genome analysis provides a platform for identifying new potential therapeutic targets for treatment of anthrax as well as the design of new vaccines," said Steven R. Blanke, an associate professor of biology and biochemistry at the University of Houston.

"The consensus is that we don't know enough about the process of infectivity," added Claire Fraser, senior author of the first paper and president of the Institute for Genomic Research (TIGR) in Rockville, Md., at a news conference Wednesday. "Certainly this is an opportunity for some fundamental breakthroughs just in understanding the biology of anthrax. The more you know about how this organism causes disease, it means you can take a much more rational, informed approach in developing new antibiotics and vaccines."

A number of antibiotics can be used against anthrax, but no medications specifically target this organism. An existing vaccine is problematic because it requires multiple doses and, even then, does not elicit the highest levels of immunity, Fraser explained. "I think we can do better, and I think this information will really accelerate the search for new vaccines," she said.

The anthrax strain used in this study, the first to be sequenced and analyzed, was taken from a Texas cow in 1981 and is virtually identical to that used in the 2001 attacks, which is known as the Ames strain.

This particular strain of anthrax is a close relative of the common soil bacterium, Bacillus cereus, which causes food poisoning and of Bacillus thuringiensis, which infects insects and is used to control plant pests.

This research, the first comparison of the three cousins, shows the anthrax bacterium may possess no more than 150 significant differences in gene structure among more than 5,000 genes as compared to its cousins (that represents about 3 percent of the total).

But it is those differences that are key when it comes to explaining the virulence of anthrax.

One key area of difference is found in the genes on small circular strands of DNA, called plasmids, in the anthrax organism, which are related to virulence and toxicity.

"The genes for lethal toxins are probably the most important reason that the cousins are less dangerous. We have found a number of genes that are not present on the close neighbors," Tim Read, first author of the first Nature paper and an assistant investigator at TIGR, told the news conference. "We're not sure whether any of those genes are important in pathogenesis, but that's a field of study that people will now take up."

Compared to its cousins, anthrax also has a surplus of genes for metabolizing proteins, suggesting that it can thrive in protein-rich environments such as animal tissues.

"Lateral transfer" of genes also occurred between the anthrax bacterium and its cousins. "These happen in nature naturally and if they are useful, the organism will keep adding to them," said Nammalwar Sriranganathan, a professor of biomedical sciences and pathobiology at Virginia Tech in Blacksburg. "It does account large segments of DNA coming into an organism." This is also known as gene-swapping.

The virulence of anthrax may also be a factor of how certain genes are expressed or function, something which is not revealed by the structural sequencing of the genome. "While the genomes of these different organisms may indicate their genetic potential to cause disease, an important key to fully understanding their virulence will be to uncover differences in the mechanisms of how these genes are used by the bacteria," Blanke said. "These studies provide the platform on which to do these studies. They suggest particular genes to look at in detail."

Although this work on the Ames strain is potentially very useful, Fraser pointed out that researchers are and need to be looking at other strains as well. "We don't want to focus on just Ames," she said. "We want to look at what will provide the broadest degree of protection."

Ames, however, was a good candidate for study because it had been weaponized and was especially virulent.

More information

For more on pathogen genomics, visit the National Institute of Allergy and Infectious Diseases. TIGR has more on the sequence of Bacillus anthracis.

SOURCES: April 30, 2003, news briefing with Claire Fraser, Ph.D., president, and Tim Read, Ph.D., assistant investigator, the Institute for Genomic Research (TIGR), Rockville, Md.; Nammalwar Sriranganathan, Ph.D., D.V.M., professor, biomedical sciences and pathobiology, Virginia Tech, Blacksburg; Steven R. Blanke, Ph.D., associate professor, biology and biochemistry, University of Houston; May 1, 2003, Nature

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