Since 2015 a Strategic Research Centre (SRC) led by Professor Jane Davies has been investigating the three challenges posed by Pseudomonas aeruginosa: finding better ways to detect the infection, understanding how it develops in the lungs of people with CF and testing new, non-antibiotic forms of therapy.
This CF Week, we’re speaking to Isaac Martin, a Clinical Research Fellow at Imperial College London, who is working with Professor Davies on this SRC and has been focussing his study on producing better treatments to help destroy the dangerous bug.
A problem faced when trying to treat Pseudomonas is that the bug can develop a protective, fortress-like structure called a ‘biofilm’. Biofilms provide physical protection for Pseudomonas and stop antibiotics from destroying them. Isaac’s research is investigating how clever groups of viruses called bacteriophages can be used to breach the bacterial fortress and kill the Pseudomonas. Isaac presented his work at the Imperial Festival in May, using balloons to represent Pseudomonas and darts to represent bacteriophages (pictured).
Tell us a bit about your research.
We’re looking to see how viruses (known as bacteriophages) can kill Pseudomonas. In particular, I am looking at how effective these viruses are in killing Pseudomonas grown in a biofilm.
So, what is a bacteriophage and what is a biofilm?
Bacteriophages are viruses that exist everywhere in nature where there are bacteria. These viruses have very specific hosts - they don’t infect human cells and only target a specific type of bacterial species. They locate their specific bacteria by recognising surface proteins on the cell, then they bind to the cell wall and release their genetic material into the bacteria. This genetic material hijacks the cellular machinery of the cell and forces it to make copies of itself. Eventually, the bacteria will burst and release hundreds of copies of the virus into the space outside of the cell, which will go on to infect more bacteria, continuing the cycle.
Biofilms are bacterial communities that act like a physical barrier around the bacteria, stopping antibiotics and the immune system from destroying them. Biofilms are made up of substances that are created and excreted by the bacteria themselves. This is thought to be one of the survival mechanisms that allows Pseudomonas to persist in the lungs of people with CF, despite oral, nebulised and intravenous antibiotics (as well as DNAse, hypertonic saline and many other advances).
What have been the outcomes so far?
We have started by investigating how effective bacteriophages are in a simple biofilm model of Pseudomonas infection. This involves growing Pseudomonas in plastic wells and allowing time for them to build biofilm communities on the walls of the plastic wells.
The results have been quite encouraging - when we add bacteriophages to conventional antibiotics in a lab biofilm model, we see a huge increase in bacterial killing. I will be submitting an abstract with some of my results to ‘CF’s Got Talent’ at this year’s UK Cystic Fibrosis Conference.
What are your next steps?
We need to investigate whether sputum is a barrier to bacteriophage therapy. The next phase of our research focuses on using an artificial sputum medium to grow biofilms that are perhaps more representative of what we would see in the lungs of someone with cystic fibrosis.
What are you hoping this research will achieve?
The ultimate aim of this project is to see whether we can deliver bacteriophages into the lungs of people with CF with Pseudomonas infection through a nebuliser device. Ideally, this would be used alongside standard nebulised antibiotic therapy.
There are still a lot of questions that need to be answered before we move on to establish if it is effective and safe for bacteriophages to be used on the human lung.
How could this research help people with cystic fibrosis?
As a clinician and a scientist, I can’t emphasize enough how important Pseudomonas aeruginosa is as a pathogen in people with cystic fibrosis. If our research has the potential to help eradicate infection in even a small number of patients, this would be of huge importance not just to lung function, but to quality of life.
To find out more about the developments in this SRC, don’t forget to buy your tickets for this year’s UKCFC. Day one is aimed at a professional audience, while day two is open to everyone with a personal or professional interest in cystic fibrosis. You will also be able to stream the entire conference – sign up to our newsletter for more updates.
Photo credit: Helen Johnson from the National Heart and Lung Institute.