How mucus sugars help protect us from harmful microbes.

This is not the sugar we might stir into our coffee, but rather complex carbohydrates — chains made up of several sugar molecules. These so-called glycans are why chemist and molecular biologist Rachel Hevey of Basel University is more fascinated than repulsed by mucus, whose consistency she describes as “kind of solid and kind of liquid.” 

This quality is due to molecules called mucins, which Hevey likens to bottle brushes: The central shaft consists of a long chain of amino acids, while the glycans form the fine bristles, extending at right angles from the shaft in all directions. “They soak up water and form a kind of gel. Glycans are what make mucus slimy,” says Hevey. Her research group is one of just a small number of teams worldwide able to produce complex glycans under controlled conditions in the lab — an important prerequisite for studying specific glycans.

How researchers produce complex sugar molecules

Synthesizing these molecules is a grueling task in the lab. “Sugar molecules have numerous identical functional groups and can therefore react with one another in many different ways,” the researcher explains. To ensure that the molecules link together only in the desired way, the researchers have to temporarily block or protect all the other functional groups. As a result, synthesizing a specific glycan can require up to 30 different reaction steps. This painstaking work can take months and requires a great deal of patience and precision. But, says Hevey: “Every glycan is like a puzzle. It’s fun to make molecules that no one has ever made before.” She and her team are unlikely to run out of work anytime soon, because glycans come in an enormous variety. 

Often, they differ only in tiny details, making them difficult to tell apart using standard chemical methods. “Over the past few years, we’ve developed a highly specialized platform for doing just that,” says Hevey.

This niche expertise puts her team in a unique position. Working with a group at Massachusetts Institute of Technology in the United States, for example, the researchers were able to investigate how molecules in our mucosal secretions protect us from fungal infections or dangerous pathogens such as the bacterium that causes cholera.

The team discovered that the gooey mixture of glycans prompts the yeast Candida albicans to form harmless, round cells when it settles in mucus and grows there. By contrast, without mucus, the fungus develops dangerous tube-shaped extensions that allow it to invade human cells and cause candidiasis. Hevey and her colleagues found three specific glycans in mucus that inhibit the formation of such tube-shaped extensions.

In another study, the researchers identified further glycans that can keep the cholera pathogen Vibrio cholerae in check. This bacterium likewise occurs in both harmless and aggressive disease-causing forms. The latter carries additional genes, including the blueprint for a toxin that can cause life-threatening diarrhea.

The blueprint for this toxin is carried on a mobile piece of genetic material known as a plasmid, which bacteria can copy and exchange with one another. If one bacterium passes on the toxin blueprint, its harmless neighbor becomes pathogenic, too. But some of the glycans in mucus prevent exactly this transformation, as Hevey and her colleagues have shown.