Nov. 21, 2001 The completed anthrax genome--expected within the next few months--should provide new clues to help explain what makes the infection a killer, and perhaps how best to fight different strains, researcher Kathryn Beauregard reports on the Science “Functional Genomics” web site.
Beauregard, of Emory University, examines what available genetic information currently tells us about anthrax, and how basic research in genomics can provide insights toward future identification, prevention and therapy efforts.
“The completion of the B. anthracis genome sequence will facilitate studies of the virulence, epidemiology, and physiology of this organism,” Beauregard writes in a peer-reviewed article appearing online 15 November 2001.
Bacteria related to the anthrax species bear trademark genes encoded in plasmids, circular molecules made of DNA that replicate independently of regular bacterial chromosomes, Bearegard explains. Toxin genes of a reputed relative, the insecticide-producing Bacillus thringiensis, are housed in these plasmids. The same goes for most of the virulence factors of anthrax-causing bacteria, Bacillus anthracis.
So far, the genetic blueprints for two anthrax plasmids have been sequenced: pXO1 and pXO2.
These plasmids, pX01 and pX02, contain genes responsible for the anthrax toxin and for resistance to the toxin, respectively. The first plasmid encodes for the three-part toxin most responsible for inflicting damage on the host, and the second encodes for resistance to attack from the host’s cells that normally engulf and destroy bacteria. The pXO1 plasmid contains a “pathogenicity island,” according to Beauregard, which are large regions of DNA that indicate virulence was acquired from unrelated organisms. The pXO1 pathogenicity island contains 44,800 nucleotides that contain the toxin genes, their regulatory elements, and the germination response genes. “Indeed, the anthrax island is flanked by inverted and nearly identical copies of an insertion sequence element. These elements serve as a footprint for previous transposition of DNA, suggesting the island was transferred in from elsewhere, possibly from another bacterial species.”
The anthrax bacteria and other species could have shared a genetic pool or transferred genetic information with each other at one time, and when certain genes combine into its own genome, “appeared to provide just the right mix for B. anthracis to kill,” Beauregard says.
Other unidentified virulence factors may exist, she continues. By comparing virulence genes of anthrax with similar genes in less destructive relatives, B. thuringiensis and Bacillus cereus (which causes food poisoning), a completed anthrax genome can tell scientists what, if any, factors were lost from attenuated anthrax strains that have been used as vaccines. In addition, the genome can help analyze anthrax gene expression and pinpoint the exact genes and proteins responsible for disease.
The genome should also make it easier to identify particular strains of anthrax, according to Beauregard, who says B. anthracis is one of the least “variable” bacterial species known. This means the difference between one strain and another is maintained by a relatively small amount of DNA. Current methods to distinguish the anthrax in recent current events involve the identification of signature strings of DNA called variable-number tandem repeats (VNTRs), mainly from the two plasmids and other fragments. “The completed genome sequence will facilitate the identification of additional VNTRs and the development of markers therein, thus making strain identification more precise in patients and in environmental samples,” Beauregard writes.
Preliminary data from tests on anthrax used in the recent public health assaults point to an interesting evolutionary history, she continues. The detected bacteria show resistance to penicillin, however, they were not engineered to make the beta-lactamase enzyme, which prevents the efficacy of penicillin. Scientists found two naturally-occurring genetic codes for the resistance enzyme.
Beauregard concludes: “It is important to remember that this work begins on a strong base of exciting research that has already identified important virulence factors that could serve as targets for future vaccine and therapy development.”
See http://www.sciencemag.org/feature/plus/sfg/ for the Functional Genomics web site at Science.
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