One Microbe’s Trash, Another Microbe’s Treasure
Microbially digested mucus provides nutrients for a pathogen
By Katherine Kelly
Edited by: Katherine Hill, Claudia Althoen, Madeline Nicol, Grace Owens-Kurtz
Mucus. This word conjures up distinct feelings and sensations, and likely a strong sense of disgust. As someone recovering from a recent cold, I have been once again intimately acquainted with this interesting bodily secretion.
Mucus is a component of our innate immune system, otherwise known as our first line of defense. This slimy substance clings to alien substances in our bodies — viruses, bacteria, dust, pollen, fungal spores — and traps them in its complex matrix.
The complex matrix consists of many individual glycoproteins — proteins with long, branched chains of sugars — known as ‘mucins.’ The interaction of sulfurs on the mucins’ sugar chains creates strong bonds between the chains, leading to tight links between individual mucins. Tight linking allows mucus to act as a fly-trap for any invaders.
In my case, mucus was hypersecreted in my lungs in response to a viral infection. Mucus’ main goal: get the invading microbes out of the lungs. Small, finger-like projections called ‘cilia’ line the lungs and help escalate mucus from the airways, which is eventually swallowed or coughed out. Although visually unpleasant, this process allows us to clear infections.
Unfortunately, this process does not function perfectly for all individuals. People with the genetic disorder cystic fibrosis (CF) often have trouble clearing mucus from their lungs, resulting in chronic lung disease. This disorder is due to a mutation in a gene, leading to a malfunctioning protein. Because of this defect, mucus thickens and becomes dehydrated, making it difficult for cilia to move mucus out.
Stagnancy of mucus in the lungs leads to longer retention time of ‘invaders.’ For individuals with CF, the most pathogenic invaders are bacteria, although fungi and viruses can also cause infections. The dominant pathogen in CF lungs is Pseudomonas aeruginosa (Psa). This pathogen seldom infects healthy individuals, yet it is a major cause of disease for those with compromised immune systems.
P. aeruginosa is environmentally ubiquitous — walk outside, find some dirt, and you would likely isolate P. aeruginosa. Because of this, there are many opportunities for exposure. However, little is known about what allows this bacterium (or these bacteria) to establish and proliferate in hosts.
A recent article from the University of Minnesota proposes a mechanism for how Pseudomonas survives and thrives in the lung. Jeff Flynn, the lead author, asked a seemingly simple question: what does Psa eat? In the CF research community, legend had it that Psa survived on the contents of dead immune cells. However, Flynn wasn’t convinced. “To my knowledge, no one has ever grown Psa on dead immune cells. Someone came up with the idea, and then it became dogma.”
The sheer amount of Psa found in the lung suggested that it encountered an abundance of nutrients in the lung — enough to support the growth of 10,000,000,000 cells! This sort of growth is consistent with feeding bacteria pure sugar, like glucose.
“I always thought there must be a better explanation. Turns out there is a REALLY abundant carbon source — the mucus,” says Flynn.
So P. aeruginosa eats the mucus? Not exactly.
Flynn tried growing P. aeruginosa on just mucin as the sole nutrient source. It grew, but not to the abundance expected based on estimates from the lungs of those infected. The question remained: what was Psa eating? The answer: digested mucus.
Flynn and colleagues then considered the ecology of the lung. P. aeruginosa was not the only microbe present. In fact, they discovered that many microbial species found in the mouth were also present in the lung, although in much lower abundance. These species are slow-growing microbes which survive by breaking down the complex mucins in saliva as a community. When Flynn fed Psa the “leftovers” of the mucin digested by the mucin fermenters, Psa grew to 10x the abundance seen when grown in pure mucin. One microbe’s trash, another’s nutritional treasure.
This trend held true when growing clinical isolates of Psa from patients and other pathogens found in the CF lung such as Staphylococcus aureus.
“From a basic science standpoint it is a really cool story that pathogenesis relies on an ecosystem,” Flynn explains. “This model moves away from the notion that ‘one organism causes one disease.’”
These results have some interesting implications, especially the idea that Psa depends on the mucin fermenters for full growth. If this food chain is vital for Psa growth, interrupting it may be a viable option for treating Psa lung infections. A new method to target Psa is important in light of increasing levels of antibiotic resistance.
“From a therapeutic standpoint, we might need to reevaluate how we treat patients. By understanding how an ecosystem supports the growth of a pathogen, we may find that the other key members of the community are ‘softer’ targets for antibiotics.”
Check out the full paper here.
Flynn JM, Niccum D, Dunitz JM, Hunter RC (2016) Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease. PLoS Pathog 12(8): e1005846. doi:10.1371/journal.ppat.1005846
