Image: courtesy of the University of Wisconsin-Madison Genome Center

Though Mad Cow remains a terrible mystery, scientists are one step closer to solving the problems posed by another bad beef bug, Escherichia coli O157:H7. This particular strain of the otherwise common and often harmless bacteria first made headlines in 1983, when it caused two outbreaks of severe gastrointestinal disease in the U.S. Now researchers at the University of Wisconsin-Madison Genome Center have sequenced E. coli O157:H7's entire genome, which they describe in today's issue of Nature. The new information reveals the bug to be remarkably wily, but may point the way to new potential treatments and vaccines.

After completing the genome sequence, Nicole Perna and colleagues compared it to that of E.coli K-12, a benign strain sequenced in 1996 by co-author and Genome Center director, Fred Blattner. "The sheer magnitude of the differences was totally shocking to us," Perna remarks. "We couldn't just zoom in on areas of difference between the two species. The changes were scattered throughout." Indeed, the two strain shared about 3,500 genes--but the virulent E.coli had 1,387 genes the harmless E.coli didn't have, and the harmless bug had 530 genes the virulent strain lacked. "What this tells us is over a relatively short time on an evolutionary time scale, on the order of five million years, you get tremendous variation in the DNA of two similar organisms," Perna notes. "This is a very 'plastic' genome."

In keeping, they discovered that the virulent strain harbored numerous so-called islands of pathogenicity, entire genetic stretches that it had adopted quickly as whole chunks, possibly from other bacteria by way of viruses. This sort of horizontal gene transfer across families of bacteria--other relatives include Samonella, Shingella and the plague-causing organism Yersinia--marks a significant finding, Blattner notes. Such a pathosphere, as he calls it, blurs the genetic lines between species. "If the pathosphere is large enough, it could be an underlying factor in the emergence of new diseases," he adds. "We are already seeing this with the ability of some bacteria to develop antibiotic resistance. We nee to be vigilant in finding the mechanisms that allow these pathogens to emerge."

Because some of the genes found in the islands are known to help E.coli O157:H7 do its dirty work--by encoding for toxins and the like--they could well serve as new targets for drug therapies. And "one of the first things we can do is improve our detection and surveillance before it becomes a public health issue," Perna adds. "We now have a far better distribution of genetic markers to help identify this in the field."