Understanding how E. coli kills cells

In the July 15 issue of the journal Genes & Development, a team of Japanese scientists have uncovered how the pathogenic E. coli bacteria cause cell death in their human hosts. These findings may open the door to the development of drugs to combat the devastation of infection by inhibiting cell death caused by the bacteria.

The E. coli bacteria include pathogenic strains that are major causes of diarrhea in developing countries, killing nearly one million children as a result of dehydration and complications from organ failure. The E. coli O157:H7 is a strain that contaminates hamburger and other foods. Ingestion of the contaminated food causes diarrhea and multiple organ failure, as a result of massive cell death in the kidneys and intestines. Nearly 76 million Americans a year get food poisoning and O157:H7 infection alone accounts for approximately 200 fatalities yearly, primarily from kidney failure.

When food is contaminated with the pathogenic E. coli, the bacteria secrete molecules called verotoxins, which are transported in the blood stream of the patient. The verotoxins are taken up by intestinal, blood, and kidney cells, which then are destroyed by the toxins. Although this general cascade had already been known, just exactly how these toxins killed the cells remained a mystery. Now, Drs. Atsushi Suzuki and Hirofumi Doi and their colleagues in Japan discovered that the verotoxins contain a short stretch of amino acids very similar to a sequence within the protein Bcl-2. Bcl-2 is a major player in a cellular process known as 'programmed cell death', in which surplus or damaged cells commit suicide to protect the whole organism from itself. This short amino acid sequence is necessary for Bcl-2 to interact with other proteins. The researchers demonstrated that one particular verotoxin binds to Bcl-2 via this short motif and triggers the cell death program in an otherwise healthy cell. The massive self destruction of the reprogrammed cells leads t

Contact: Atsushi Suzuki
Cold Spring Harbor Laboratory

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