How does cholera toxin enter a cell?
Sugar-coated proteins on colon cells are key to the uptake of the toxin from cholera-causing bacteria.
Cholera is a serious diarrheal disease that can be deadly if left untreated. It is caused by eating food, or drinking water, contaminated by the bacterium Vibrio cholerae. This bacterium can survive passage through the acidic conditions of the stomach. Inside the small intestine, V. cholerae attaches to the intestinal wall and starts producing cholera toxin. The toxin enters intestinal cells, causing them to release water and ions, including sodium and chloride ions. The salt-water environment created inside the intestine can, by osmosis, draw up to a further six liters of water into the intestine each day. This results in the copious production of watery diarrhea and severe dehydration.
Cholera toxin is composed of six protein subunits, including five copies of cholera toxin subunit B (CTB). CTB subunits help the uptake of the toxin by intestinal cells, and it has long been reported that CTB subunits attach to intestinal cells by binding to a cell surface molecule called GM1. CTB subunits have a high affinity for GM1, yet recent work suggests CTB may not bind exclusively to GM1; one or more additional cell surface molecules may be directly involved in cholera toxin uptake.
Amberlyn Wands, Akiko Fujita and co-workers now reveal that numerous cell surface molecules are recognized by CTB, and that these molecules can assist cholera toxin uptake by host cells. Glycoproteins — proteins that are marked with sugar molecules — were shown to be the primary CTB binding sites on human colon cells, and it was the glycoprotein’s sugar component, not the protein itself, that interacted with CTB. Wands, Fujita and co-workers discovered that in particular glycoproteins containing a sugar called fucose were largely responsible for CTB binding and toxin uptake. Together these findings reveal a previously unrecognized mechanism for cholera toxin entry into host cells, and suggest that fucose-containing or fucose-mimicking molecules could be developed as new treatments for cholera.
To find out more
Read the eLife research paper on which this eLife digest is based: “Fucosylation and protein glycosylation create functional receptors for cholera toxin”(October 29, 2015).
