by Jenny Zheng
figures by Rebecca Clements

With winter soon coming to an end (hopefully), many of us have been plagued by seemingly endless hacking that’s accompanied by phlegm, a type of mucus produced by the respiratory tract. The body starts feeling better after a week of sickness, but even after that “hell-week,” one final foe has to be dealt with: the phlegm. It’s such a nuisance that we probably just wished that all of our mucus would go away, but this overlooks the fact that the creation and coughing up of phlegm is a way for our lungs to get rid of infectious microbes. If we manage to think beyond that disgusting phlegm lodged in our throats, we can start to appreciate that our bodies constantly produce mucus to help keep us healthy. In particular, mucus can assist our immune systems by acting as a natural filter for the bacteria we interact with constantly.

So, what is mucus?

Mucus is a protective substance that’s excreted from multiple areas of the body, such as the mouth, sinuses, throat, lungs, stomach, and intestines (Figure 1). Mucus itself consists of multiple constituents, but its major component is a substance called mucin. The mucins in mucus can work as a selective barrier, lubricant, or viscous material depending on their structure. When mucin structure and production is normal, mucus protects surfaces all over our body, which helps us live alongside many different microbes. However, disease can ensue when mucin structure and production are abnormal.

Figure 1: Protective mucus is found all over the body. The zoomed-in image on the right is a cartoon depiction of the surfaces of those body parts. The pink blobs are epithelial cells, which are the outer layer of cells in many parts of the body. Mucus (the yellow cloud above the pink blobs) covers the cell’s surface and contains mucins (brown lines) that define its properties.

How can mucus prevent disease?

Professor Katharina Ribbeck’s research group at MIT wants to understand the benefits of mucus, and it has uncovered interesting properties of mucins as a result. Ribbeck’s group has purified natural mucus from a pig stomach to obtain a mucin known as MUC5AC. This pig-derived mucin is related to the MUC5AC found in multiple parts of the human body, such as the respiratory tract, stomach, gallbladder, and female reproductive organs. Since pigs and humans are closely related, the function of their respective MUC5ACs should be similar. Using liquids containing MUC5AC, they investigated the interaction between mucin and microbes in our lungs and guts, and whether the mucins might be preventing some of these microbes from causing disease.

One such microbe is a bacterium called Pseudomonas aeruginosa, which lives in our lungs and is often harmless when found in healthy individuals. However, it can cause lung infections in patients with a disease called cystic fibrosis, which is characterized by abnormal mucus production. These infections are exacerbated when P. aeruginosa starts forming sticky groups of bacteria known as biofilms on the surfaces of the lungs. Biofilm formation is often associated with increased virulence (i.e. the ability of a microbe to cause disease), and groups of bacteria in biofilms are more resistant to antibiotics. Therefore, biofilms cause infections to be more aggressive and more difficult to treat. Can we find a way to prevent biofilm formation in order to help these patients?

Voila! Ribbeck’s group found that MUC5AC can possibly prevent lung infections by making surface attachment more challenging, which can prevent P. aeruginosa biofilm formation. Conventional wisdom would lead us to believe that mucus suppresses biofilm formation by trapping bacteria, rendering them immobile, and preventing aggregation. On the contrary, Ribbeck’s group determined that the true mechanism may be opposite of this intuitive thought. In the more viscous MUC5AC solution, they saw that bacteria actually move faster. This increased motility (ability to move) decreases biofilm formation because moving cells are less likely to stick together (Figure 2), which renders the bacteria less dangerous. We are lucky to have mucus protecting us from potentially nasty bacteria.

Figure 2: Mucus disrupts biofilm formation. In healthy individuals (the left box), the bacterium, P. aeruginosa (blue cylindrical objects with tails) can move around because the mucin itself binds to the bacterium, acting as a signal for the bacterium to increase motility through the use of flagella (the tails in the picture). In the diseased state (right box), with either no mucus or abnormal mucus, the cells can stick together and form biofilms.

Another microbe made less dangerous by mucus is a yeast called Candida albicans, which can live in places like the gut, mouth, and vagina. C. albicans can cause an infection called candidiasis (a.k.a. thrush or yeast infection when in the mouth or vagina, respectively), but it is found in the gut or mouth of 80% of adults without causing any harm. However, if a healthy person contracts another sickness that weakens the immune system or changes mucus production, C. albicans can either aggregate in biofilms or form hyphae, which allow the yeast to invade human cells (damaging the cells and providing the yeast access to the bloodstream). When C. albicans is allowed to overgrow in these forms, the result can be fatal. C. albicans’ virulence is tied to its ability to invade cells through hyphae and biofilm formation, so Ribbeck’s group tested the effect of multiple mucins (including MUC5AC) on C. albicans behavior. Much like for P. aeruginosa, they determined that mucin exposure decreases virulence by mitigating biofilm formation. They also observed that it prevents hyphae formation, which further diminishes virulence.

Diagnostic potential

We have seen that mucus is highly beneficial to our health when its structure and production are normal. However, there are times when people get sick and mucin production becomes abnormal. A sick person may be producing atypical mucus, which may manifest as changes in either the amount or structure of its constituent mucins. When mucin’s structure changes, its ability to dampen the virulence of pathogens can be weakened, or the strength (characterized by viscosity and fibrosity) of the mucus itself can change. In these cases, even though mucin may not be protecting us as effectively, it may be used as an indicator of an illness or increased susceptibility to disease. One example of using mucus as a diagnostic tool is the analysis (also done by Ribbeck’s group) of the structural properties of cervical mucus to assess the risk of pre-term birth. If cervical mucus is structurally weaker (thinner and more stretchy) and more permeable—which would allow more bacteria to travel through the mucus—then pregnant women have a higher risk of pre-term birth; stronger mucus, on the other hand, indicates a lower risk of pre-term birth. Just by observing mucus, doctors can more accurately predict which pregnant women should be watched for pre-term birth.

The future

This article about mucus is just the tip of the iceberg; both the lessons we can learn from mucus and its potential uses seem unlimited. Maybe one day we will be able to explore the uncharted territory of healthy donors providing mucus to help prevent P. aeruginosa biofilm formation in cystic fibrosis patients who produce abnormal mucus. This could potentially go a long way in making antibiotic treatments more effective and reducing the chance of infection in the first place.

The more I learn about mucus, the more I realize how important it is. So, the next time we cough up some phlegm, maybe remember how mucus helps us out and appreciate what comes up.

Jenny Zheng is a second-year Ph.D. student in the Department of Molecular and Cellular Biology at Harvard University.

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