Cholera is a devastating disease that reached and maintained epidemic proportion throughout much of the 1800’s. Although many infected individuals are asymptomatic or have mild conditions, the symptoms of those with epidemic cholera are extreme diarrhea, nausea and vomiting, dehydration, and cardiovascular and neuromuscular complications due to the lost of important electrolytes.
Treatments for Cholera:
1. In 1892, Waldemar Haffkine, a Russian bacteriologist, working at the Pasteur Institute in France, created the first cholera vaccine from an attenuated form of the bacterium. He successfully tested his treatment on himself, and subsequently moved to India and vaccinated over 50000 people there.
2. Tetracycline, created in the 1940’s was the first antibiotic treatment for cholera. Antibiotic treatments have little effect on the spread of cholera through and likely enhance the development of resistant forms of the bacteria.
Cholera Toxin’s Structure:
Rong-Guang Zhang, et. al. determined the 3D structure of cholera toxin (CT) using x-ray crystallography. Overall, CT is an hexametric complex composed of a single wedge-shape. A subunit polypeptide containing 240 amino acids, and a pentameric B subunit, with each polypeptide having 103 amino acids .
Cholera Toxin’s Molecular Effects
1. Once Vibrio cholerae is ingested and has successfully navigated to the small intestine, it secretes the cholera toxin (CT).
2. The B subunit is responsible for CT binding. After binding, endocytosis of the entire toxin proceeds, and culminates in its retrograde movement to the endoplasmic reticulum. At this point, the disulfide bond connecting A1 and A2 is cleaved, and the A1 subunit is released into the cytoplasm.
3. The free A1 toxins, after binding NAD, catalyze the ADP-ribosylation of the cell’s G-proteins, which in turn permanently activates the membrane bound enzyme adenylate cyclase (AC), causing cellular ATP to be converted to cAMP.