Mucus, microbes, and mimicry

When one gets an infection like strep throat, they’re sometimes treated with antibiotics—drugs that kill the pathogens causing the sickness. But as antibiotic resistance emerges as a global health emergency, scientists around the world are diligently investigating new solutions to treat infections. According to Dr. Laura Kiessling and Dr. Katharina Ribbeck, the answer may be in our mucus. “Most people don’t look at their snot and think, ‘Wow, that’s going to be a great therapeutic!’” Dr. Kiessling says. “But mucus is actually a critical line of defense for our immune systems. It’s a natural barrier that lines over 200 square meters of our body, selectively filtering nutrients in and toxins out—and it has the unique ability to disarm infectious pathogens.”

Mucus is composed of mucins—long, thread-like polymers with hundreds of sugar molecules called glycans attached to them. Dr. Ribbeck notes that these glycans are the key to suppressing harmful pathogens and preventing biofilm formation—the clumpy, slimy layers formed by bacteria that cause 80% of infections. “Glycans are what enable mucins to disarm bacteria, rather than kill them,” she explains.

Her findings enabled Dr. Kiessling to build mimetic, synthetic versions of these molecular structures to treat and prevent infectious diseases—an intriguing contrast to antibiotics. “Our partnership requires very close synergy,” says Dr. Ribbeck. “We each have unique perspectives that we bring to the design and evaluation of the mimics. I identify which features of natural mucins ‘tame’ the pathogens, and Dr. Kiessling focuses on distilling these features in synthetic mucins using creative chemistry.” Adds Dr. Kiessling, “It’s a beautiful collaboration—together, we’re discovering enormous potential for disrupting pathogens by mimicking nature’s strategies. We’re moving further away from a warfare analogy in treatment—we’re not killing the bacteria, which only pressures them to evolve and become resistant. Instead, we’re taming normally pathogenic microbes so we can live with them.”

Fighting a sticky perception

“Mucus is often thought of as a waste product, and it’s something many view with disgust,” says Dr. Ribbeck. “Our work is generating a paradigm shift toward the understanding that mucus is a sophisticated material with powerful abilities to manipulate microbial behavior, so writing grants to fund this kind of research can be a challenge.” She and Dr. Kiessling needed to illustrate that mucus is an essential facet of human physiology and potentially represents a major change in the way infections are treated. “Mucus is an unsung hero and cornerstone of our health—if we can make even a small change to its image, we’ll have accomplished something special,” she adds.

The functions of mucus haven’t been well studied either, meaning Dr. Ribbeck and Dr. Kiessling are at the forefront of conceptual development. “We are building out an entirely new field as we conduct our research,” says Dr. Kiessling. “Chemists typically focus on studying small molecules and discovering new antibiotics—not many people have been interested in mimicking the features of mucus. It’s an intellectual shift, and the Bose grant has allowed us to nucleate our team and work cohesively to accomplish this complex chemistry.”

Clearing the way for synthetic slime

Dr. Ribbeck’s research over the last decade has illustrated that mucins can effectively attenuate the virulence of numerous problematic pathogens, while Dr. Kiessling successfully illustrated methods to mimic mucin-like proteins on immune cells over 20 years ago. Now, both scientists are excited to work together to expand the field even further, especially as they apply their earlier research to generate mimics of the mucins that occur in the gut. “The beauty of what chemistry allows us to do can’t be overstated—it enables us to create things beyond what nature gives us and build these mimetic, synthetic mucins,” says Dr. Kiessling.

According to Dr. Ribbeck, mucins’ potential could go far beyond preventing pathogens. As she continues to investigate the specific functions of glycans, she is discovering an expansive library of bioinformation. “Mucins could change the way we interface with all kinds of microbes—from viruses to fungi to parasites,” she says. “This project represents an incredible opportunity to contribute something new to a young field.”

Mucin mimics are the real deal

The research went as smooth as snot. “From the outset” said Dr. Kiessling, “we were focused on how mucus protects our bodies from bacterial infections by separating the microbes inside us from the rest of our tissues.” Working with cholera cells in a petri dish, they introduced mimics of mucin and observed the reaction. “The experiment showed that the mucins effectively toned down the toxins in the cholera cells,” said Dr. Ribbeck. “By blocking the toxins, the mucin mimics demonstrated how—had they been implanted in a human—they would have protected human tissues from the cholera.”

The research team didn’t stop there. Another experiment showed that these very same mimics can inhibit the growth of a common vaginal pathogen that causes preterm births; they have filed a patent request for the latter solution. “Our next steps are to see to what extent we can broaden the applicability of this bacteria-blocking agent to manage other important pathogens,” said Dr. Ribbeck. “Our experience working with glycans is also motivating us to get deeper into glycoscience.” Adds Dr. Kiessling, “We’re grateful for the Bose grant, which helped to strengthen our working relationship with each other, and is also helping to catalyze linkages between researchers interested in the role of glycans in human health.”