Cystic Fibrosis (CF) affects around 10,500
people in the UK. The genetic mutation that causes CF leads to the build-up of
thick mucus in the airways of the lung. This mucus cannot be cleared without
physiotherapy, and people with CF are vulnerable to respiratory infections that
are difficult to treat with antibiotics. Various different microorganisms can
coexist within the mucus and cause infection.
To study infections of the CF lung we need
accurate laboratory models. The problem is that bacteria behave differently
when grown in artificial models, compared to inside a living body.
Historically, scientists have overcome this by using live animal models. But,
apart from obvious ethical implications, animal models are complex, expensive
and, in the case of CF, not very accurate. Pulmonary infection symptoms in a CF
mouse are quite distinct from those seen in humans. In mice, lung infection
with Staphylococcus aureus rapidly leads to the formation of abscesses (1); a rare phenomenon in people with
CF. S. aureus is often found in
the sputum of people with CF but doctors debate whether it actually causes lung
damage. In fact, clinicians are starting to question if using antibiotics to
clear S. aureus from the lung might do more harm than good (2, 3).
Some larger animals have respiratory systems
more closely related to humans. Pig lungs in particular have similar anatomy to
our own. Thankfully, we do not have to experiment with live pigs, instead we
use pig lungs that are a waste product of the meat industry, and usually only
used for pet food. We cut small cubes from the airways and place these in
plastic dishes surrounded by artificial mucus, with a similar chemical
composition to mucus in CF lungs. Using this method, we are able to accurately
model infections caused by Pseudomonas aeruginosa,
a bacterium which infects most adults with CF, and is linked with worsening
symptoms (4). We are also investigating how S.
aureus might live in the lungs of people with CF. In our model it does not
damage lung tissue or cause the abscesses seen in mice.
We want to explore different bacterial species
in the model in more detail. Might S. aureus really colonise mucus
without triggering harmful symptoms? We also want to study how different
bacteria interact. For example, even if S. aureus is not harmful alone,
does it encourage more dangerous bacteria, such as P. aeruginosa, to grow? Or, conversely, could the presence of S.
aureus protect the lung? The answers to these questions will have important
implications for future clinical treatment.
As well as understanding infection, an accurate
yet cheap lung model could provide a simple way to test drug delivery and
efficacy –speeding up the development of treatments for a range of respiratory
diseases. Or, it might help us understand the effect of air pollution or
e-cigarette vapour on lungs. There are multiple research uses, ultimately, we
have shown that, by using a waste product from the meat industry, a realistic
alternative to live animal models is possible, affordable and sustainable.
1. Bragonzi A. Murine models of acute and chronic lung infection with cystic fibrosis pathogens. Int J Med Microbiol. 2010 Dec;300(8):584-93.
2. Ratjen F, Comes G, Paul K, Posselt HG, Wagner TO, Harms K. Effect of continuous antistaphylococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis. Pediatr Pulmonol. 2001 Jan;31(1):13-6.
3. Smyth AR, Rosenfeld M. Prophylactic anti-staphylococcal antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2017 Apr 18;4:Cd001912.
4. Harrison F, Diggle SP. An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms. Microbiology. 2016 Oct;162(10):1755-60.
Esther is currently working as a research technician at Warwick University. Having previously gained her PhD at Bristol Centre for Antimicrobial Research and Evaluation and The University of the West of England. She has experience in developing laboratory models of chronic infection and is particularly interested in poly-microbial biofilm infections and their impact on antibiotic resistance. When she isn’t working at the laboratory bench, she can be found, relaxing, by painting or hiking outdoors with her three lively boys. She is passionate about bridging the gap between science and the creative arts and her blog on how to inspire scientific curiosity in children, through creative activities, can be found at facebook.com/scienceandthesink