Washington: Researchers have identified an underlying biochemical mechanism that helps make cholera toxin so deadly, often resulting in life-threating diarrhea.
Two groups of scientists at the University of California, San Diego, worked on fruit flies, mice and cultured human intestinal cells to study cholera toxin, produced by the highly infectious bacterium Vibrio cholerae.
They discovered the toxin exerts some of its devastating effects by reducing the delivery of proteins to molecular junctions that normally act like Velcro to hold intestinal cells together in the outer lining of the gut.
The UC San Diego researchers found that cholera toxin acts by two entirely distinct, but cooperating mechanisms to produce diarrhea. In addition to increasing the efflux of chloride ions through a protein channel called CFTR, it weakens cell junctions to allow a rapid outflow of counterbalancing sodium ions and water between the cells.
The scientists showed that many of the effects of the cholera toxin on the gut could be reversed by genetic manipulations that bolster the delivery of proteins to these junctions.
Understanding this novel mechanism of cholera action could also have important implications for other disorders of intestinal barrier function such as Crohn's disease, colitis and celiac disease.
The study is published in the journal Cell Host and Microbe.