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Molecules in mucus subdue microbes to make them harmless

Mucus contains sugars that can interfere with bacteria’s communication and behavior, a new study found.

Melvin Sanicas
October 17, 2019 @ 9:23 pm

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More than 200 square meters of our bodies — including the digestive tract, lungs, and urinary tract — are lined with mucus. Far from being a gross waste product, this slippery secretion produced by, and covering, the mucous membranes serves an important physiological purpose.

It has been established that mucus is the body’s security bouncer physically trapping pathogens, toxins, and fine particles like dust and pollution. The cells of the immune system in the mucus then attack and neutralize the invading germs before they get the opportunity to spread throughout the body and cause infection. In some instances, mucus is coughed up or expelled – which is the body’s way of forcing the pathogens out of the body. Mucus also lubricates the eyes so they can blink and the throat so it can swallow. It also serves as a lubricant under the skin’s surface to help minimize friction between the organs.

New research at the Massachusetts Institute of Technology (MIT) and published in Nature Microbiology shows one of mucus’s unexpected beneficial properties: mucus contains sugars that can interfere with bacteria’s communication and behavior, effectively stopping the formation of dangerous, tough biofilms and making them harmless.

The research was funded by the National Institute of Biomedical Imaging and Bioengineering, the National Institutes of Health, the National Science Foundation, the National Institute of Environmental Health Sciences, and the MIT Deshpande Center for Technological Innovation.

Katharina Ribbeck and her colleagues study compounds called mucins in mucus. Mucins are long polymers, or molecular chains, densely studded with sugars. They “look like mini bottlebrushes,” Ribbeck said, except bristling with sugar molecules where whiskers would be.

“What we have in mucus is a therapeutic gold mine,” said Ribbeck, the Mark Hyman, Jr. Career Development Professor of Biological Engineering at MIT. “These glycans have biological functions that are very broad and sophisticated. They have the ability to regulate how microbes behave and really tune their identity.”

Ribbeck and others have shown that mucus can stop microbes from binding to surfaces. Researchers focused on how glycans were interacting with an opportunistic microbial pathogen called Pseudomonas aeruginosa, the bacterium commonly causing serious infections in people with weak immune systems and cystic fibrosis patients.

They found that when bacteria were exposed to glycans isolated from mucus, they were disarmed; the microbes stopped attaching to or killing host cells, halted production of toxic molecules, and microbial genes that are involved in bacterial communications weren’t expressing. The new study is the first to “identify that the glycan component” — that is, the sugars grafted to the mucins — “is responsible for suppressing antagonistic microbial behaviors.”

They now plan to study the impact of individual glycans out of hundreds that can be found in mucus. They also want to investigate how glycans affect other kinds of pathogens like Candida albicans and Streptococcus bacteria. They already know that glycans can stop Streptococcus from sharing genes, a primary way that drug resistance spreads among microbes.

“What we find here is that nature has evolved the ability to disarm difficult microbes, instead of killing them. This would not only help limit selective pressure for developing resistance, because they are not under pressure to find ways to survive, but it should also help create and maintain a diverse microbiome,” Ribbeck says.

Scientists, including Ribbeck, are also looking into the development of artificial mucus, which might be a new approach to fighting pathogens that does not involve traditional antibiotic drugs.

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