The shiny secrets that could loosen the grip of a beastly bacterium

January 18, 2002

Mass killer 0157:H7 is so deadly it earned a place in the Guinness Book of Records . Geoff Watts reports on research that could turn the tables and make its life more hazardous

Though neither memorable nor elegant, the enigmatic sequence "0157:H7" made a brief impression on our collective consciousness during 1996. This was the year that the common gut bacterium E. coli killed 20 people who had eaten a church lunch at Wishaw in Strathclyde. The first victim, an 80-year-old, died on November 26, nine days after the meal. This and the subsequent deaths earned the episode a mention in the Guinness Book of Records as the deadliest outbreak attributable to the bacterium responsible: a strain of E. coli known in the arcane world of bacterial nomenclature as 0157:H7.

The Escherichia coli family comprises a multitude of such strains, most of which live happily in our guts and do us no harm. They even do some good by manufacturing useful nutrients. 0157:H7 is one of a minor-ity that are pathogenic.

But the scientists are fighting back. A couple of researchers at Imperial College, London, have exposed its secret - and they think that this may offer a new way of taming the beast.

In fact it is cattle, not humans, that bear the brunt of the microbe's assaults. But if it does find its way into our guts, its effects can be lethal. Besides causing diarrhoea and the other symptoms of food poisoning, it produces a toxin that spreads throughout the body and can lead to kidney failure. For some reason, Scotland seems to get more than its fair share of these encounters.

To do its worst, E. coli cannot just float freely in the intestine. It needs to attach itself to the cells lining the gut wall. Like a human climber on a rock face, its future depends on getting a firm hold. Climbers will grasp whatever projections, crevices and other handholds are there to be exploited. Similarly, most bacteria that need to stick to a cell hitch themselves to certain molecules that form a natural part of its surface. These "receptor" molecules, as they are known, find themselves acting inadvertently as docking points for the microbe.

But some climbers choose not to rely on what nature has provided. They come prepared, carrying pitons and hammers, and create their own points of attachment. Remarkably, E. coli  0157:H7 has developed a similar trick.

Gad Frankel and Steve Matthews, of the department of biological sciences at Imperial College, have been making a close study of the E. coli family members and their modus operandi . A protein on their surfaces, called intimin, forms the mooring rope. It makes the actual attachment to the docking sites on their host's cells. But 0157 does something else to maintain a really firm hold. "It produces its own receptor and injects it into the host cell," Matthews says.

Having control over the design of the receptor - the piton, in climbing terms - as well as the mooring rope probably serves to make the bug's grasp really tight. So how does E. coli contrive to perform such a trick?

Frankel explains: "Bacteria have a kind of pump that can push proteins out of them and through a complex molecular structure that acts like a syringe needle. There are many bacteria we know that use a system such as this. Mostly they inject materials that subvert normal cell function for the benefit of the bacterium. This is the first example we know of a bacterium that injects its own receptor."

As soon as the receptor material - a protein - has been pumped into the host's intestinal cells, it integrates into their surfaces where it offers a powerfully attractive binding site to any intimin molecules - and so, of course, to any bacteria on which those intimin molecules are located. In short, having created their own handholds, the microbes promptly grab them.

Matthews is studying the structure of intimin, hoping to understand why it sticks so tightly. "It gives you an opportunity for designing molecules that might interrupt the process," he says. And this, of course, is the hoped-for practical payoff: a new way of tackling E. coli - a vaccine, perhaps.

"The reservoir for these bacteria is cattle," Frankel points out. "So the way to get rid of this nasty infection is at the source by developing a veterinary rather than a human vaccine. If you get rid of the infection in cattle, it won't enter the food chain and reach humans." So far, the work has been supported by the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the charity Action Research. Now, Frankel says, there is also commercial interest in the project.

Others are looking at 0157, too. Recently, a group at the University of Southampton showed that even at the temperatures normally used for food storage, the microbe could survive on stainless-steel work surfaces for more than five weeks. On copper, however, the bugs were all dead after just 14 hours. So, pure copper work surfaces in future for Delia Smith, Jamie Oliver, Marco Pierre White and the rest? Hardly. But a copper alloy that retained this bactericidal action might be practicable. One way or another, life may soon be more hazardous for 0157:H7.

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