Details of how killer E Coli works

Unusual Traits Blended in Germany E. Coli Strain


Published: June 22, 2011

The E. coli bacteria that killed dozens of people in Germany over the past month have a highly unusual combination of two traits and that may be what made the outbreak among the deadliest in recent history, scientists there are reporting.


University Hospital M�nster/Institute for Hygiene

The E. coli O104:H4 strain has a pattern that looks like a stack of bricks on cultured intestinal epithelial cells.

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An investigator at an organic farm in the village of Bienenbuettel, north west of Berlin, on June 6.

One trait was a toxin, called Shiga, that causes severe illness, including bloody diarrhea and, in some patients, kidney failure. The other is the ability of this strain to gather on the surface of an intestinal wall in a dense pattern that looks like a stack of bricks, possibly enhancing the bacteria’s ability to pump the toxin into the body.

The thought is that the bacteria started out being able to aggregate with the brick pattern and then were infected with a bacterial virus that gave them the Shiga toxin, said Dr. Matthew K. Waldor, an infectious-disease expert at Harvard Medical School who was not connected with the new research.

With the two traits combined in one strain of E. coli bacteria, “now they are highly virulent,” Dr. Waldor said. The new findings, by a team led by Dr. Helge Karch of the University of Münster, were published Wednesday in the journal Lancet Infectious Diseases. They result from two days of fevered work to characterize the bacteria causing the illness that raced through Germany in May.

Experts in the United States praised the German scientists’ work. The work and the entire outbreak are “a real game-changer,” said Dr. Philip I. Tarr, a professor of pediatrics and an expert in gut infections at the Washington University School of Medicine in St. Louis. Dr. John Mekalanos of Harvard called the paper “extremely important.”

Other Shiga-producing bacteria adhere to the lining of the gut much less avidly, in diffuse clumps, not bricklike walls, Dr. Tarr said. And other strains of E. coli that do attach tightly to the gut do not make Shiga toxins. The combination of the two traits in one E. coli strain may be what makes this one so lethal.

Microbiologists knew, of course, that E. coli can be deadly; outbreaks in the United States involving tainted hamburger or vegetables have led to kidney failure in 5 to 10 percent of victims. And they knew that the most vulnerable were the very young and the very old.

But the recent outbreak, which has been traced to contaminated bean sprouts grown on a German farm, was different. As of June 20, it had sickened 2,684 people with diarrhea and 810 with kidney failure. Thirty-nine people died. The proportion with kidney failure — 25 percent — was “extraordinary,” Dr. Waldor said.

Moreover, the victims tended to be young and middle-aged women.

Still, Dr. Michael T. Osterholm, an epidemiologist at the University of Minnesota who has investigated food-borne disease outbreaks in the United States, said that while there was no doubt that the German outbreak was horrendous, he questioned whether as many as 25 percent had kidney failure. The percentage depends on the denominator — the total number of people infected. And many, especially at the beginning of the outbreak when the numbers were highest, were not tested, Dr. Osterholm said. Labs had to look for Shiga toxin in stool, he said, and that “is hardly ever done.”

But whether it was 25 percent of the infected or something less, the number of victims was sobering. The hospital in Münster was only mildly affected, compared with others in northern Germany. Yet Dr. Karch said that even there, “within a few weeks, 20 patients had to be dialyzed.” Now, he added, although the epidemic is dying out, at least 100 people will need kidney transplants or will have to undergo dialysis for the rest of their lives.

Dr. Karch, an expert in E. coli, infections, got the first stool samples on May 23. Over the next few days, more and more samples flooded his lab, 50 to 100 a day. “You can’t imagine,” he said.

He isolated the strain that was causing the illness and analyzed it to determine that it was strain O104:H4. Then he began investigating the bacteria’s DNA. First he determined what kind of Shiga toxin it made. Then he did adherence tests and found that the bacteria stuck to surfaces in the bricklike pattern. It is an unmistakable phenomenon: “Once you see it you will never forget it,” Dr. Karch said.

He posted the results and provided detailed information so most labs that had a suspicious stool sample could analyze it immediately and see if the stool contained O104:H4 bacteria. Until he posted that information, most labs would be at a loss. The strain is so rare that there are no standard tests to find it.

Dr. Karch also realized that the O104:H4 strain had been seen before in bloody diarrhea and kidney failure, but only on rare occasions — first in Germany in 2001, then sporadically in a few other countries. And in each outbreak, at most a few people were ill.

Why, then, was the German outbreak so widespread, and where did the bacteria go between outbreaks?

Many experts assumed the bacteria lived in animals, probably cattle. That is where the strain that usually causes severe illness, E. coli O157:H7, is found. And that is why it has spread all over the world as animals, and their meat, transmit it to humans. In fact, Dr. Karch said, E.coli O157:H7 is thought to have traveled to Europe from America in 1610, spread by cattle.

But the strain that caused the German outbreak does not seem to live in animals.

“I think it is human-specific,” Dr. Karch said. And that increases the mystery of where it goes between outbreaks.

Dr. Karch thinks it smoldered in human populations, causing mild illnesses in most and occasionally causing severe disease. Then, somehow, it was passed to the bean sprouts by someone who harbored the bacteria. And since sprouts are eaten raw, they were highly infectious.

The strain is so rare, Dr. Karch said, that those infected had no immunity. An epidemic caught fire.

Women may have been the primary victims, Dr. Karch speculates, because they are more likely to eat sprouts.

He himself does not like sprouts, he said, though his wife does. Aware that sprouts have always been “a high-risk food” for bacterial illnesses, he will not touch them unless they have been cooked.

A version of this article appeared in print on June 23, 2011, on page A5 of the New York edition with the headline: Scientists Find 2 Unusual Traits Blended in German E. Coli Strain.