Danial N. answered • 01/14/21
MD Candidate with an MS in Physiology/Biophysics
Vibrio Cholerae is a gram negative rod-shaped bacterium. These bacteria can cause the disease known as cholera when we drink infected water and some of the bacteria in the infected water make it past the acid environment of the stomach and into the small intestine. The bacteria V. Cholera produce and release Cholera Toxin, which is a hexameric (6 subunit) structure, consisting of 1 catalytic A subunit, and 5 binding B subunits. On the surface of the small intestine, the toxin binds a membrane sphingolipid on enterocytes (type of small intestine cells), called GM1 ganglioside, via its B subunits. Once the B subunits bind GM1, the A/B toxin is endocytosed (brought into the cell), where the A subunit binds the alpha g-protein in it's GTP-bound state (ON state). The A subunit ADP-ribosylates an arginine residue on the alpha g-protein which stabilizes the GTP-bound/ active state. Because the G-protein is now stuck in its active state, it continuously activates adenylate cyclase, which then increases the cellular levels of cAMP. cyclic AMP, or cAMP, activates PKA (protein kinase A). PKA activates the opening of Cl- channels and inhibits the opening of Na/H antiporters. The net effect of this is that NaCl (sodium chloride aka table salt) leaks out from the cell and into the lumen of the small intestine. Following the rules of osmosis, water follows NaCl. If you can imagine, by constantly losing salt to the lumen, and therefore constantly losing water, (massive diarrhea) the infected person becomes severely dehydrated and will likely die if not treated promptly. (Treat infection, replace fluids)
