Breakthrough could lead to E. coli vaccine

by Stephen Forgacs

Staff writer

A new understanding of how E. coli bacteria bond to host cells may lead to the creation of a vaccine against strains of the bacteria that cause potentially fatal diarrhea in children, as well as hamburger disease, salmonella and dysentery.

A research team in UBC's Biotechnology Laboratory, led by Prof. Brett Finlay, has discovered that enteropathogenic Eschericia coli (E. coli), which causes a million infant deaths worldwide a year, inserts a chemical advance party into a host's intestinal cells to prepare a hospitable landing site for the bacteria.

Researchers previously believed that the receptor, a protein which allows the E. coli bacteria to adhere to a host's intestinal cell walls, existed within the host cells.

"All our biochemical data said it was a host membrane protein," says Finlay. "We thought the bacteria come in, stick to the cell, and then send signals that get the cell warmed up so it can bind properly. But the bacteria are far more devious than that."

Finlay found that rather than making use of a host protein, the bacteria fire a soluble bacterial protein into the host cell membrane. The protein is then modified in the host cell membrane to form a perfect landing site for intimin, a bacterial surface molecule that binds with the host cell surface.

"That's completely unprecedented. We know of no other pathogen that inserts its own receptor."

Finlay calls the process, in which a soluble bacterial protein is inserted into a host cell membrane, "biochemically completely absurd."

Ironically, the bacteria's self-sufficiency may prove its downfall. Having identified the bacterial protein, Finlay says it may take only one or two years to develop vaccines that will prevent the transmission of the bacterial protein to the host cell. This would prevent E. coli from binding to the host cell, forcing it to be passed from the system.

Vaccines could be used to prevent the infection of cows with the bacteria, and thus prevent the transmission of the bacteria to beef consumers. Or, vaccines could be used to inoculate humans against the bacteria.

"What's become apparent is the machinery that E. coli uses to shovel these proteins out is very similar to the machinery used by many other pathogens such as salmonella, shigella, which causes dysentery, and yersinia, which causes bubonic plague and major food poisoning in Vancouver."

Finlay calls the discovery "typical science." On a hunch, Brendan Kenny, who was doing post-doctoral work in the Biotechnology Laboratory, tracked a bacterial protein which appeared to be inserted into host cells.

"The scepticism in the lab was huge at first," says Finlay. "The concept has never been explored before. Luck, skill, perseverance -- it has all the elements of a typical science story.

"Yet this is probably one of the biggest things we've ever found in the whole field because it will now make people consider that pathogenic organisms, bacteria, parasites, maybe even viruses, can basically encode their own receptor. Then they can put their receptor in a host cell and capitalize on it."

Earlier this year, Finlay received $275,000 US from the Howard Hughes Medical Institute to further research into the genesis of bacterial infections -- innovative work combining genetics, biochemistry and molecular and cell biology. He is a member of the Canadian Bacterial Diseases Network (CBDN) of the Networks of Centres of Excellence.

Finlay looks at molecules which aid and abet the passage of disease-causing bacteria in the human body. His focus has been on salmonella and E. coli.