Study of the Week: How P. Aeruginosa Resists Cystic Fibrosis Treatment

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies

We previously published about this research in a story titled “Researchers have Uncovered a Mechanism Through Which Cystic Fibrosis Drugs Become Ineffective,” which can be found here. The study was originally published in the research journal Cell Reports. You can view the full study text here.

The team of researchers in this study were affiliated with the University of Montana, with Laura Jennings as lead author.

What Happened?

For patients living with the rare lung disease cystic fibrosis, the possibility of infections in the lungs is always a threat. Many patients take antibiotics for much of their lives, but sometimes this treatment isn’t very effective. One type of bacteria that is dangerous for these patients is Pseudomonas aeruginosa. This bacteria is common in cystic fibrosis patients and can also opportunistically infect diabetic ulcers and burn wounds. It’s a difficult infection to get rid of and even repeated courses of antibiotics may not be effective.

The scientists sought out to figure out why P. aeruginosa was so effective in resisting typical antibiotic treatment. What they found was both surprising and remarkable: the bacteria was producing a carbohydrate based coating around itself that was protective against antibiotics. This coating is an aspect of how this species aggregates in the lungs. These aggregates, called biofilms, hold the individual cells together, forming an extracellular matrix. This matrix is comprised of exopolysaccharides which the scientists call Pel and Psl.

The aggregation of the bacterial cells is dependent on these exopolysaccharides. The researchers propose that Pel interacts with the anionic host polymers that are present in the cystic fibrosis sputum. In addition, Pel binds to extracellular DNA (eDNA), which allows it to evade digestion from the treatment and increase overall tolerance of the bacteria to antibiotics. This also provides a protective effect against therapies that are meant to make the sputum in the lungs thinner. However, the protective effect did not occur with all antibiotics.  

About Cystic Fibrosis

Cystic fibrosis is a type of genetic disorder that can have impacts throughout the body, but it is most characterized by the build-up of abnormally thick, sticky mucus in the lungs. This mucus becomes a fertile breeding ground and habitat for potentially infectious bacteria. Many patients must take antibiotics for much of their lives. This disorder is caused by mutations of the CFTR gene. Symptoms of cystic fibrosis include progressive decline in lung function, lung and sinus infections, coughing up mucus, fatty stool, poor growth, infertility in males, clubbed digits, and digestive problems. Treatment includes antibiotics and medications or procedures intended to maintain lung function. More useful treatments for the disorder have been introduced in recent years. Lung transplant is an option when lung function declines severely. Life expectancy ranges into the 40s and 50s with good care. To learn more about cystic fibrosis, click here.

Why Does it Matter?

The findings from this study carry substantial implications for the future treatment of cystic fibrosis. All in all, the treatment outlook in this disease has improved steadily in recent years, and a significant number of patients can respond effectively to disease-modifying therapies and improve their lung function. However, the risk of infection remains and not all patients are reaping benefits from the newest treatments.

This means that therapies to thin mucus and fight off bacterial infections will continue to be a mainstay of cystic fibrosis treatment for the foreseeable future. The revelations from this study about how a common pathogen P. aeruginosa is able to reduce the impact of treatment and protect itself means that the antibiotic of choice may need to change for these patients if outcomes are to improve.

The description of the protective mechanism may also open the door for the development of new treatments or the use of different antibiotics that haven’t been widely introduced in the treatment of cystic fibrosis. Ultimately, this discovery also provides a starting point for future research that could one day lead to a new treatment that is capable of circumventing the protective measures of P. aeruginosa and allowing for better control of the long-term chronic infections that it can cause in patients living with this disorder.

Check back the Monday of each week for the next installment in this series.

Share this post

Share on facebook
Share on google
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email