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Gut's hospital bug defence found

By James Gallagher Health reporter, BBC News
Clostridium difficile bacteria Researchers show how the body stops C. diff from being toxic

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The way cells in the gut fight off toxins produced by a hospital bug has been discovered by US researchers.
Writing in Nature Medicine, they showed how a chemical - GSNO - deactivated a toxin from Clostridium difficile which causes inflammation and diarrhoea.

They hope to use their findings to develop a treatment for C. difficile.

A specialist in the bacterium said the discovery was "exciting", but any treatment was still a long way off.

C. difficile is one of many bacteria which can live in the human gut without causing health problems.

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Understanding how this mechanism deactivates toxins provides a basis for developing new therapies that can target toxins directly”
Dr Jonathan Stamler Case Western Reserve University
 
A course of antibiotics, which wipes out other bacteria in the gut, can allow C. difficile to multiply and run rampant in the bowels.

They produce large numbers of toxins which enter the cells lining the bowel. This damages the cells resulting in inflammation, cramps, fever, diarrhoea and blood-stained stools.

It is particularly a problem in hospitals as the bacteria can spread, and many patients could be taking antibiotics or have a weakened immune system.

In hospitals in England there were 10,414 C. difficile infections during the financial year 2010-11, down from 33,442 in 2007-08.

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The whole toxin is unable to penetrate cells so it needs to cleave off a smaller chunk.

Scientists have identified the chemical GSNO - S-nitrosoglutathione - which is produced by the bowels in response to inflammation. It can bind to the toxin, preventing cleavage, so the toxin cannot enter cells.

One of the researchers Dr Jonathan Stamler, from the Case Western Reserve University, said: "Understanding how this mechanism deactivates toxins provides a basis for developing new therapies that can target toxins directly and thereby keep bacterial infections, like C. diff, from spreading."

In experiments on mice, the study showed giving the chemical orally increased survival. Researchers now want to begin clinical trials.

The report's lead author Prof Tor Savidge, from the University of Texas, believes the technique could be used on other infections.

"Along with its potential to provide a much-needed new approach to treating Clostridium difficile infection, the discovery could be applied to developing new treatments for other forms of diarrhoea, as well as non-diarrheal diseases caused by bacteria," he said.

Prof Nigel Minton, from the Clostridia Research Group at the University of Nottingham, said: "This is an exciting discovery.

"Anything that can add to our scant arsenal of available treatments for combating this devastating disease is an important step forward.

"Having said that, one imagines that an actual therapeutic based on this discovery is some way off, either from being developed, and more importantly, from entering the clinic."

http://www.bbc.co.uk/news/health-14589385
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