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How E. coli bacteria become deadly: The making of a monster

Like an unexpected and unwelcome guest, pathogenic E coli burst onto the national scene nineteen years ago. Escherichia coli -- E. coli for short -- is a harmless bacteria that lives in the gut of humans. Scientists have studied it for decades. It was one of the first organisms to have its genome fully sequenced at the turn of the new century. No more scary than Mary Poppins, E. coli has been a basic part of genetics grad student education for fifty years.

This pretty picture changed forever in 1982, on one horrible weekend when hamburgers made from tainted beef killed party-going children. Public health scientists quickly identified what had contaminated the beef: E. coli bacteria. Not the harmless kind we were used to, but a new deadly form. Eaten by the children, this E. coli caused a severe bloody diarrhea and, in the more serious infections, lethal kidney damage. It is now a common cause of food poisoning, producing diarrhea in 73,000 people in the United States each year. Of those, about 2000 are hospitalized, and 60 die.

What had happened to transform a harmless bacterium into a killer? Biologists thought they knew. This sort of thing had happened before. The bacteria Vibrio cholerae usually exists in a harmless form, but a second, virulent (disease-causing) form occasionally arises, responsible for the deadly disease cholera. The deadly form is created by a virus that infects V. cholerae. When the virus enters the bacterial cell, it brings with it a gene that encodes a diarrhea-causing toxin. The toxin gene becomes part of the bacteria’s chromosome, converting what was a benign bacterium into a killer.
Scientists surmised that E. coli bacteria became deadly in 1982 in much the same way as V. cholerae, gaining a toxin gene from an infecting virus or from some other bacterium. This was a logical guess, but, as it turns out, not a good one.

Two weeks ago Drs. Fred Blattner and Nicole Perna of the University of Wisconsin and a team of researchers announced in the journal Nature the sequencing of the full genome of the deadly form of E. coli, a strain technically labelled O157:H7. This same team had already sequenced the harmless variety in 1997, and expected the DNA makeup of this dangerous strain to be similar, with perhaps a toxin gene or two added. “How different can they be?” Perna asked in an Associated Press interview

Very different, it turns out. The DNA of O157:H7 E. coli was one quarter longer than the harmless variety. It somehow had managed to obtain a host of new genes, the blueprints for a family of deadly modifications designed to aid infection.

The harmless and deadly strains share more than 4000 genes, the genetic “core” that defines the species E. coli. But interspersed among the core of O157:H7 are 177 new chunks of DNA containing 1,387 genes. “The sheer magnitude of the difference was totally shocking to us,” Perna said.

They weren’t just any old genes, either, these new ones. It was as if E. coli had deliberately set out to acquire genes that would help it better infect humans. Some of the new genes make enzymes that protect O157:H7 from being digested by stomach acid. With this improvement, less than a hundred O157:H7 cells can pass unharmed through the stomach and start an intestinal infection; several hundred thousand cells are required for successful infection by the harmless variety. Eight clusters of genes specify hairlike projections that allow the bacterium to grab onto the cells of the intestinal wall like grappling hooks. Other genes produce syringes that inject glue-proteins that stick the bacteria to any intestinal wall cells they reach. Still other genes make the deadly toxins that cause bloody diarrhea. All in all, an unpleasant package.

How did this happen? Scientists have known since 1947 that E. coli bacteria can swap genes with other bacteria, but no one had guessed until now how very much they do so. In addition, some of the added genes of O157:H7, including the toxin genes, seem to have been introduced by viruses, just as happens in V. cholerae.

So how did the E. coli growing in cattle accomplish this monstrous transformation? Evolution acts strongly among bacteria that swap genes around, favoring mutations that cluster growth-promoting genes together. The clusters then bud off of the chromosome, creating infectious DNA bits called plasmids. Plasmids can pass from one bacterial cell to another. That is why the new genes of O157:H7 are found in clusters -- they arrived that way, on plasmids.

This troublesome package of infection-promoting genes is made up of just the sort of changes that foster success among bacteria living in a mammal’s gut. Natural selection rewards success where it finds it, and doesn’t ask our opinion or permission. Evolution doesn’t know hero or monster, only survival.

Whatever other little surprises evolution has in store for us, what scientists are learning today about diseases like deadly E. coli will surely make us better able to respond to new threats when they appear in the future, as they surely will, unexpected and unwelcome. Knowledge will always be our best defense.

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