Definitions & Key takeaways

Vibrio cholerae is a bacterium that causes cholera, a severe and contagious diarrheal disease. Cholera is transmitted through contaminated water or food and is most common in areas with poor sanitation and limited access to clean drinking water.

Some strains produce cholera enterotoxin, which acts on the intestinal epithelial cells in the small intestine, causing over-activation of the enzyme adenylate cyclase. This leads to an increase in the intracellular levels of cyclic AMP (cAMP) in the intestinal cells, which in turn leads to the secretion of large amounts of water and electrolytes into the intestinal lumen, resulting in the characteristic watery diarrhea of cholera.

Patients most often present with voluminous, profuse, watery diarrhea, vomiting, and dehydration, all of which lead to fatal dehydration and electrolyte imbalances. Treatment involves rehydration therapy to replace all the fluids and electrolytes that are lost through diarrhea. In severe cases, antibiotics such as tetracyclines, ciprofloxacin, or trimethoprim-sulfamethoxazole may be necessary.

Cholera is a contagious infection caused by the bacteria Vibrio cholerae, which can in turn cause severe gastroenteritis and excessive watery diarrhea for several days.
Rapid dehydration and electrolyte imbalances can be fatal as suspected in the deaths of James K. Polk, the 11th President of the United States; and Charles the Tenth, King of France.
V. cholerae is a gram-negative, curved bacteria which looks like little red or pink comma-shapes on a gram stain.
It’s positive for oxidase and grows in alkaline media. It has pili and a single polar flagellum, kind of like a tail, at one end which it uses for movement through the gastrointestinal tract.
It’s a facultative anaerobe so that means it can undergo respiratory and fermentative metabolism. Transmission of V.
cholerae typically occurs through a fecal to oral route. This includes consuming untreated sewage water, and anything that comes in contact with it, like raw or undercooked fish including shellfish; and improper hygiene, like a lack of hand washing after a bowel movement.
Cholera tends to be more common in developing countries and places lacking advanced sanitation and sewage treatment facilities, with high rates in some locations in Africa and South America.
People who have low gastric acidity or have an O-blood type are particularly at risk for a severe infection. Now, when V.
cholerae enters the stomach it shuts down protein production to conserve energy and nutrients, and to survive the acidic environment.
But once V. cholerae is in the intestines, it uses its flagella to move toward the intestinal walls; propel through the mucous layer on top of the epithelial cells lining the intestines; and attach to the finger-like cellular projections, called villi, on the surface of the epithelial cells.
There, V. cholerae can begin to multiply and produce toxins.
And though V. cholerae does not enter the epithelial cells itself, the toxins do and they can cause a lot of trouble.
Now, the exact toxins produced can depend on the strain of V. cholerae.
Some strains produce toxins that won’t cause any, or maybe just mild clinical symptoms. But some strains produce cholera enterotoxin, also called choleragen, which is most often the cause significant clinical symptoms.
When cholera enterotoxin enters the epithelial cells, it leads to the ADP-ribosylation of the Gs alpha subunit of G-protein.
So, this causes the G-protein to becomes permanently activated and it keeps activating a membrane-bound protein called adenylate cyclase.
This protein in turn leads to an overproduction of the intracellular secondary messenger protein, cyclic adenosine monophosphate, or simply cAMP.
Increase in cAMP causes chloride channels on the cells to increase the secretion of chloride into the lumen while inhibiting the channels that let sodium and chloride back into the cell.
So, the abnormally high levels of luminal sodium and chloride disrupt the osmotic balance between the intestines and surrounding tissue; and water, bicarbonate, and potassium rush into the lumen of the intestines as a result.
This can cause symptoms like vomiting and voluminous amounts of watery diarrhea containing extremely high concentrations of sodium, potassium, chloride, bicarbonate; as well as high levels of live V.
cholerae ready to infect another individual. There could also be flecks of the mucous layer of the intestine which looks similar to rice in water.
Typically, there is no fever, pain or cramping. And while the incubation time for V.
cholerae can take hours, to 2-3 days; severe dehydration and depletion of electrolytes can happen within 4 to 12 hours of the first bout of diarrhea or vomiting.
These imbalances can lead to symptoms like disorientation, dry mouth, swollen tongue, sunken eyes, cold clammy skin, or shriveled and dry hands and feet.
Other, even more severe, fatal complications can come from depleted electrolytes and water in the blood. Like low levels of bicarbonate can cause metabolic acidosis with deep and labored breathing called Kussmaul breathing.
Or low levels of potassium can cause muscle dysfunction including leg cramps, weakness and abnormal heart rhythms. And low chloride and sodium can cause headaches, poor balance, disorientation, seizures and coma.
Finally, severe dehydration can cause hypovolemic shock with a significant decrease in blood pressure. Diagnosis is typically made by a stool sample growing V.
cholerae on a thiosulfate-citrate-bile salts-sucrose agar. But even before a definitive diagnosis can typically be made, the first line of treatment is to rapidly replace the lost water and electrolytes with rehydration salts either orally or intravenously.
In cases of mild to moderate diarrhea, this type of supportive therapy is enough of a treatment course and the diarrhea may resolve on its own in about 3 to 7 days.
But more extreme cases may require antibiotics. In this case, the stool culture can be helpful in deciding which antibiotics would be most effective against the infecting strain, and may include tetracyclines, ciprofloxacin, ofloxacin, furazolidone, or trimethoprim-sulfamethoxazole.
So, to recap: Cholera is a contagious, severe gastroenteritis caused by the gram-negative Vibrio cholerae bacteria. It’s route of transmission is fecal to oral through consumption of contaminated sources like water and shellfish.
Some strains produce cholera enterotoxin at the surface of intestinal epithelial cells which leads to the over-activation of cAMP by permanently activating Gs alpha.
Patients most often present with voluminous “rice-water” diarrhea that quickly leads to dehydration and electrolyte imbalances that can be fatal if not rapidly treated with rehydration salts.