Illustration of a woman suffering from cholera

The biology behind cholera

Iona Twaddell looks at the science of the waterborne disease cholera

There are an estimated 3–5 million cases of cholera, a disease caused by the bacterium Vibrio cholera, each year. It is passed on through drinking water that has been contaminated with faeces from someone infected with the bacteria. Cholera causes vomiting and diarrhoea, leading to severe dehydration.

What are ion channels?

Ion channels are membrane proteins that, when open, allow ions (charged atoms) to pass through them into or out of the cell. Several different things can open ion channels: some ion channels open because of changes in voltage, and others open because of a chemical (ligand) binding to them. In cholera, dehydration occurs because of chloride ion channels.

A type of chloride ion channel called the cystic fibrosis transmembrane conductance regulator (CFTR) normally allows chloride ions to flow out of cells. In small intestine cells the CFTR channel is used to adjust water levels: a higher concentration of chloride ions outside the cell will cause water to leave by osmosis. Cholera disrupts this process.

How does cholera affect ion channels?

The cholera bacteria produce a toxin that is made of six protein subunits. The cholera toxin binds to receptors on cells in the wall of the small intestine and activates cyclic AMP (cyclic adenosine monophosphate, a messenger molecule), increasing the number of cyclic AMP molecules in the cell.

As CFTR channels are activated by cyclic AMP, the increased concentration of cyclic AMP causes the CFTR channels to open and stay open. This means that chloride ions (Cl) move out of the cell into the lumen (the inside of the small intestine tube). Sodium ions (Na+) are attracted to the negative chloride ions, so they also leave the cell.

With more ions in the lumen, the lumen has a lower water potential. This makes water leave the cells lining the lumen by osmosis, down the concentration gradient. The cells lose a lot of water, which causes severe dehydration, and the increased water in the small intestine causes watery diarrhoea and vomiting.

How do you treat cholera?

Oral rehydration therapy treats the dehydration caused by cholera. During severe diarrhoea, the body loses a lot of water and some essential ions. Patients are given oral rehydration solution, which contains mainly water along with some ions that the body might have lost through diarrhoea, such as potassium.

Oral rehydration solution also contains glucose. This provides energy and helps the sodium–glucose cotransporter protein, which absorbs sodium into the cell much better if glucose is also present. The glucose in the oral rehydration solution ensures that the protein will bring as much sodium as possible into the cell. Bringing more sodium into the cell reduces its water potential, causing water to re-enter the cell from the lumen by osmosis.

What do cholera and cystic fibrosis have in common?

The CFTR channel is also involved in cystic fibrosis (as you might have guessed from its name). However, in cystic fibrosis the CFTR proteins are ineffective and don’t open, leading to the opposite situation to that which occurs in cholera.

In cystic fibrosis, chloride ions build up in the cells instead of moving out through the channels, so water doesn’t move out by osmosis. This is a problem because in the cells most affected, the water is needed outside the cells to dilute mucus. This mucus lines the tubes of most systems, including the respiratory, digestive and reproductive systems. Without dilution, the mucus blocks these passageways and causes severe problems.

Cystic fibrosis is caused by a genetic mutation, and this mutation might actually protect against cholera. A cystic fibrosis mutation that causes an incorrectly shaped CFTR channel would reduce the effects of cholera because it would prevent so many chloride ions leaving the cell and building up in the lumen.

When was cholera discovered?

Cholera has an interesting history. Although humans have been getting cholera since the times of ancient Greece, the fact that cholera is caused by contaminated water wasn’t discovered until the 1850s when John Snow investigated a cholera epidemic in London.

Epidemiology is the study of the patterns of disease. John Snow was one of the first people to look at patterns of disease in the modern era – for this, he is known as the father of (modern) epidemiology.

In 1854 he mapped out where the people who got cholera lived, and he realised that they all lived clustered around a certain water pump: the Broad Street pump. Snow took the handle off the pump, which prevented people from using it, and the cholera outbreak stopped. It was later discovered that sewage had infected the pump, leading to the cholera cases. Snow’s systematic observation had helped uncover the cause of cholera, even before anyone knew about the bacteria involved.

Lead image:

An illustration of a woman suffering from cholera, which can turn the skin blue-grey as a result of dehydration. 

the lost gallery/Flickr CC BY

References

Questions for discussion

  • What are the problems with putting too much glucose in oral rehydration solution? And too little?
  • Who discovered the bacteria responsible for cholera? How and when did they do it?
  • Cholera outbreaks can occur after natural disasters such as earthquakes, and during wars and times of civil unrest. Why?

About this resource

This resource was first published in ‘Proteins’ in January 2014.

Topics:
Cell biology, History, Health, infection and disease, Biotechnology and engineering
Issue:
Proteins
Education levels:
16–19, Continuing professional development