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Protective molecules present in mucus could prevent cholera

Science Writing, 12 Dec. A team of researchers has identified molecules in the mucus that are capable of blocking cholera infection by interfering with the genes that make the microbe harmful.

These molecules, known as glycans, are one of the main components of mucins, the gelling polymers of mucus.

The team, led by researchers at the Massachusetts Institute of Technology (MIT), has identified a specific type of glycan that can prevent Vibrio cholerae produce the toxin that often causes severe diarrhea.

The results have been published this Monday in the EMBO Journal.

The authors believe that if these glycans could be transported to the site of infection, they could help strengthen the mucosal barrier and prevent symptoms of cholera, which affects up to 4 million people a year.

And because glycans disarm bacteria without killing them, they could be an attractive alternative to antibiotics, the study suggests.

“Unlike antibiotics, to which resistance can develop quite quickly, these glycans do not actually kill bacteria. They only appear to turn off gene expression of their virulent toxins,” explains Benjamin Wang, one of the study’s lead authors. .

In recent years, Katharina Ribbeck’s team, who led the study, has discovered that the mucus present in a large part of the body plays a key role in controlling microbes.

For example, his lab has shown that glycans can inactivate bacteria such as Pseudomonas aeruginosa and yeast Candida albicanspreventing them from causing harmful lung infections.

The new study has focused on Vibrio choleraea microbe spread by contaminated drinking water that infects the gastrointestinal tract causing severe diarrhea and dehydration.

Vibrio cholerae occurs in many strains but the microbe only becomes pathogenic when infected by a virus called a CTX phage.

But for this “toxigenic conversion” to occur, the CTX phage must bind to a receptor on the surface of the bacterium known as the toxin co-regulated pilus (TCP), the paper explains.

Working with mucin glycans purified from the porcine gastrointestinal tract, the MIT team discovered that the glycans suppress the bacterium’s ability to produce the TCP receptor, so that CTX phage can no longer infect it.

The researchers also showed that exposure to mucin glycans dramatically alters the expression of many other genes, including those needed to produce cholera toxin.

When the bacteria were exposed to these glycans, they produced almost no cholera toxin.

The team is now looking for ways to deliver synthetic mucin glycans, possibly along with antibiotics, to sources of infection.

By themselves, glycans cannot attach to the body’s mucosal linings, so Ribbeck’s team is looking into attaching them to polymers or nanoparticles to target them.

The researchers plan to start with lung pathogens, but hope to apply this approach to intestinal pathogens such as Vibrio cholerae.

“We want to learn how to deliver glycans by themselves, but also together with antibiotics, when a dual approach is needed. That’s our main focus now, because we see that many pathogens are affected by different glycan structures,” he concludes. EFE

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