Mutations in just a few genes can turn a benign dirt bacteria into the deadly form of anthrax that was used to kill five people in the fall of 2001, researchers report. Scientists compared the deadly pathogen's genetic makeup with those of its two closest, and less dangerous, relatives. The findings, published today in the journal Nature, should help elucidate how virulence evolved and help researchers mount a better defense against the potential bioterror agent.

Previous research yielded maps of large portions of B. anthracis's genome. In particular, scientists knew that the main differences between B. anthracis and its harmless soil bacteria cousins came from its two plasmids, which are small circles of DNA that lie outside of the chromosome. In B. anthracis, these plasmids (known as pXO1 and pXO2) carry genes that account for much of its toxicity to animals and humans. Now Tim Read of the Institute for Genomic Research (TIGR) and his colleagues have analyzed the five million DNA bases that comprise the entire chromosome of B. anthracis. They also compared the results with the genomes of B. cereus, which can cause food poisoning, and B. thuringiensis, which is employed as a pesticide. The team found only 150 significant differences among the more than 5,000 genes that comprise each of three genomes, including several key changes that could contribute to B. anthracis's harmfulness. Read notes that B. anthracis's virulence "may have come mainly from horizontal gene exchanges, more so than by mutations within the genome."

A second comparison of the B. anthracis genome with that of B. cereus, carried out by Natalia Ivanova of Integrated Genomics and her colleagues, appears in the same issue of Nature. The findings hint that the common ancestor shared by the bacteria favored a carnivorous diet and may have been a parasite or dined on dead flesh. Because the genomes of all three species are so similar, the researchers posit that the ability to cause disease depends mainly on which genes are turned on in each organism. "Deciphering the anthrax genome is important to a wide range of biomedical and biodefense research," Claire M. Fraser of TIGR notes. "The genome sequence will benefit research projects to find targets for new drugs and vaccines as well as to improve anthrax detection and diagnosis."