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What allows C. difficile to survive so well in the gut?

According to some experts, Clostridium difficile infections are ever on the rise and becoming increasingly difficult to treat.

This means that researchers need to find new and better ways of targeting this stubborn bacterium.

Among other symptoms, C. difficile can cause diarrhea, which can range from mild to extremely severe.

In the most extreme cases, the infection can even lead to a person’s death.

Since infections with C. difficile are so difficult to treat, researchers strive to find out what gives this bacterium its resilience, hoping that it might lead to more effective therapies.

Recently, a team from the London School of Hygiene and Tropical Medicine in the United Kingdom made a new and important discovery: C. difficile releases a special compound that allows it to gain ground over gut bacteria and to establish a strong presence in the gut environment.

These findings are now published in the journal PLOS Pathogens.

The compound ‘allied’ with C. difficile

C. difficile infections often appear after a person has followed a treatment with antibiotics, because these drugs work by essentially killing bacteria. Unfortunately, antibiotics do not only destroy the bacteria that cause harm.

Antibiotics also disrupt the balance of the gut microbiota, which contains many types of bacteria that are harmless and promote or sustain the health of the intestines. When this happens, C. difficile sometimes takes hold — and fighting it is often very complicated.

The researchers note that one reason why this bacterium may be able to maintain its dominance in the gut is that it can produce a compound called para-cresol (p-cresol), which affects the growth of many microorganisms in the gut.

For the first time, researcher Lisa Dawson and team found that the release of p-cresol allows C. difficile to prevail over other bacteria found in the gut.

Working with a mouse model, the scientists observed that p-cresol targets other gut bacteria — including Escherichia coli and Klebsiella oxytoca — and prevents them from growing. These bacteria would otherwise compete with C. difficile, disrupting its expansion; however, the compound’s effect prevents them from doing so.

The scientists also revealed that mutant strains of C. difficile — which could not produce p-cresol — were weakened and therefore less able to populate the gut following the initial infection.

“[W]e have identified that the major gut pathogen [C. difficile] produces the bacteriostatic agent [p-cresol] which helps control the intestinal microbiota and provides C. difficile with a competitive growth advantage particularly after the consumption of antibiotics,” explains Dawson.

These findings, she suggests, may allow researchers to develop therapies that target and neutralize the mechanism that lends this bacterium some of its resilience.

This unique attribute of the pathogen may provide a novel drug target to reduce C. difficile infection.”

Lisa Dawson

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