In recent years, scientists have found evidence that mucus is not just a physical barrier that traps bacteria and viruses, but it can also disarm pathogens and prevent them from causing infections. A new study from MIT reveals that glycans are responsible for most of this microbe-taming. There are hundreds of different glycans in mucus, and the MIT team discovered that these molecules can prevent bacteria from communicating with each other and forming infectious biofilms, effectively rendering them harmless.
"What we have in mucus is a therapeutic gold mine," says senior author Katharina Ribbeck. "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."
In the study, published today in Nature Microbiology, Ribbeck wanted to test whether glycans were involved in mucus' ability to control the behavior of microbes. These sugar molecules, a type of oligosaccharide, attach to proteins called mucins, the gel-forming building blocks of mucus, to form a bottlebrush-like structure. Mucus-associated glycans have been little studied, but Ribbeck thought they might play a major role in the microbe-disarming activity she had previously seen from mucus.
To explore that possibility, she isolated glycans and exposed them to Pseudomonas aeruginosa. Upon exposure to mucin glycans, the bacteria underwent broad shifts in behavior that rendered them less harmful to the host. For example, they no longer produced toxins, attached to or killed host cells, or expressed genes essential for bacterial communication.
"We've seen that intact mucins have regulatory effects and can cause behavioral switches in a whole range of pathogens, but now we can pinpoint the molecular mechanism and the entities that are responsible for this, which are the glycans," Ribbeck says.
Pseudomonas aeruginosa is just one of many opportunistic pathogens that healthy mucus keeps in check. Ribbeck is now studying the role of glycans in regulating other pathogens, including Streptococcus and the fungus Candida albicans, and she is also working on identifying receptors on microbe cell surfaces that interact with glycans.
Image: A scanning electron microscope (SEM) image of the polymer network that makes up mucins. Image courtesy of Katharina Ribbeck