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German outbreak caused by previously unknown strain

June 2, 2011 By Marian MT Turner This article courtesy of Nature News.

Genome sequence gives clues to microbe's sticking power.

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The bacterium responsible for the current outbreak of enterohaemorrhagic Escherichia coli (EHEC) infections in Germany is a strain that has never before been isolated in humans. The discovery, announced today by the food safety office of the World Health Organization (WHO) in Geneva, Switzerland, means that the infection could prove unusually difficult to bring under control.

Scientists in Germany are feverishly analysing the genome sequence of the bacterium, and have found clues as to how this strain — which has so far infected more than 1,500 people and killed 18 — is making so many people ill.

The bacteria are relatively unusual in that they produce extended-spectrum ß-lactamases — enzymes that render the bacteria resistant to many different antibiotics. Patients with E. coli infections are not typically treated with antibiotics anyway, because the bacteria are thought to respond to the medication by increasing production of the Shiga toxin, which can lead to the life-threatening complication haemolytic–uremic syndrome. But antibiotic resistance might have helped the bacteria to survive and persist in the environment.

"EHEC outbreaks usually only last around two weeks, but this outbreak has been going on since 1 May or earlier," says Angelika Fruth, a microbiologist based in Wernigerode who works for the Robert Koch Institute, the federal agency responsible for disease control. The number of new cases is still rising, suggesting that whatever their source, the bacteria are still infecting people.

That source remains a mystery. A case–control study of female patients and healthy women, conducted by epidemiologists from the Robert Koch Institute, revealed that the ill women were more likely than the controls to have eaten tomatoes, cucumbers and salad vegetables prior to contracting the disease, but exactly which vegetables are responsible, if any, is unclear. Early reports that the outbreak originated in cucumbers imported from Spain were later shown to be incorrect — the cucumbers contained the bacterial toxins, but not the bacteria responsible for the ourbreak themselves.

Fresh vegetables are still the prime suspect, but Flemming Scheutz, head of the WHO Collaborative Centre for Reference and Research on Escherichia and Klebsiella in Copenhagen, suggests that the bacteria might not have originated in the food chain at all. "This strain has never been found in any animal, so it is possible that it could have come from straight from the environment into humans".

Lothar Wieler, a veterinary microbiologist at the Free University of Berlin, cautiously agrees with this theory. In addition to the antibiotic-resistance genes, the bacteria contain a gene for resistance to the mineral tellurite (tellurium dioxide).

Tellurium oxides were used as antimicrobial agents against diseases such as leprosy and tuberculosis before the development of antibiotics. Some strains of bacteria may have evolved resistance to tellurium during its historical medical use, or after its use in the mining and electronics industries increased its presence in the environment. According to Wieler, the strain's resistance characteristics could point towards an environmental source, such as water or soil.

Mature target

The ongoing genetic characterization of the strain might also reveal why the bacteria is mostly infecting adults, and women in particular. EHEC infections usually occur in children, and affect boys and girls equally. Initial theories suggested that young adult women are the people most likely to purchase, handle and consume salad vegetables. "This is still our only explanation for this demographic," says Wieler. But he suspects that the strain might have biological characteristics that make adults more susceptible to the infection.

One telltale sign is that the strain does not contain the eae gene, which codes for a protein called intimin, an adhesion protein that allows the bacteria to attach to cells in the gut. Eae-negative E. coli have been specifically associated with adult infections before, although it is still unclear why this particular protein is more effective in adult guts than in those of children.

Gad Frankel, a microbiologist at Imperial College London, suspects that the genome of this strain will reveal more information about the adherence mechanisms of E. coli. "Some pathogenic bacteria don't just stick to cells in our guts, they also have active adherence mechanisms to stick to some vegetables," says Frankel.

It is possible that the strain has evolved a combination of adhesion proteins that makes it particularly hard to remove from food, or for the human body to eliminate. "This outbreak has shown we need to be prepared to deal with emerging strains with properties that give them enhanced virulence," says Frankel.

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