Trust Venture and Innovation Award funds research exploring new ways to study CF lung infections
Background to Jemima’s research
In the last decade, genetic methods for detecting infection-causing bugs have started to be used for lung samples from people with CF. The results show that people with CF usually grow a mixture of many different infection-causing bugs in their lungs at the same time. These are known as polymicrobial infections. How specific bugs cause infections and how they respond to treatment can be affected by how they live alongside a mixture of different bugs. But not enough is known about how the bugs live together, and more research is needed to find out.
A constant challenge for lab-based researchers is to mimic what’s happening in the body as closely as possible. With the new knowledge that a mixture of different bugs were growing in the lungs of people with CF at one time, new lab methods were needed to study how the bugs interacted with each other.
Jemima, a PhD student in Prof Welch’s research group, is studying the interactions of mixtures of infection-causing bugs in the lab. To do this, she’s using a specially designed lab set up, known as a ‘continuous flow bioreactor’. Here she explains what it is and how she’s using it in her research.
We grow the bugs together in one bottle (known as a ‘flask’ in the lab). The liquid that the bugs grow in is called ‘artificial sputum media’ and it is made from a recipe of over 30 chemicals. The flask is being constantly stirred and kept at body temperature (that’s 37°C ). There are two plastic tubes that have their ends in the liquid in the flask, one tube is slowly removing the liquid to a waste pipe, and the other tube is adding new, fresh liquid into the flask.
The movement of the liquid in and out of the flask is very carefully controlled by a pump. The pump has rollers inside which compress the tubing. As the rollers rotate, they force the liquid to move through. Running at steady speed, less than two teaspoons of liquid per hour are changed in the flask. This is the same speed that sputum is cleared from the lungs of people with CF!
It is the exchange of liquid using the pump that makes this set up different to other lab set ups, and makes it possible to study how a mixture of different bugs grow together. Using this set-up, we are able to grow several microbial species together over time periods of several days. In other lab set ups using ‘batch’ cultures, one bug takes over within a couple of hours of starting the experiment. We know that this isn’t what happens in the lungs of people with CF.
How do the most resistant strains of Pseudomonas aeruginosa affect the neighbourhood?
For my PhD, I am investigating the ways in which Pseudomonas aeruginosa (P. aeruginosa ) adapts when it infects the lungs of people with CF, what drives these adaptations, and their impact on how the bacteria lives in the lungs.
A few specific strains of P. aeruginosa are found in a lot of CF lung infections, which indicates that they may have adapted to living in the thick and sticky mucus in the lungs of people with CF. However, we still don’t know much about how these strains have adapted themselves.
I'm investigating how these adaptations happen, how the presence of these strains of P. aeruginosa affects the balance of which bugs are present in polymicrobial infections, and also how they affect response to antimicrobial treatment.
I’m currently using the continuous-flow culture system to grow P. aeruginosa alongside the other species for a long period of time. Then I will carry out genetic analysis to see what adaptations the bacteria has made in response to the presence of other infection causing-bugs.
What difference could this make to people with CF?
I hope that in the future, my results can inform doctors about more effective combinations of antibiotics to use to treat CF lung infections, considering all of the bugs growing in the lungs and how they will react to treatments.
We’ve awarded over 100 VIAs to advance CF research. These collaborative grants help tackle lung infections, antimicrobial resistance, and other challenges.
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