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What did the project achieve?
"Our work has uncovered important new information about why chest infections can be so hard to treat in children with cystic fibrosis," says Dr Tanmay Bharat of the University of Oxford. "We hope this will one day lead to new drugs that will improve the effectiveness of antibiotic treatment at combating these infections – reducing lung damage and improving life expectancy for people with the condition."
Around 10,800 people in the UK - including over 4,700 children – are living with an inherited condition called cystic fibrosis.1 Sadly, two people will lose their lives to the disease every week.2 A major cause of illness and death is persistent chest infection from a bacterium called Pseudomonas aeruginosa (P. aeruginosa). These bacteria form structures called biofilms that help them to avoid destruction by antibiotics and the immune system.
Using cutting-edge electron microscopy, the researchers studied the structure of a virus called Pf4, which is released by P. aeruginosa bacteria, in order to understand its role in forming the biofilms that aid their survival.
“We revealed the structure of the Pf4 virus at the atomic level and showed it assembles into highly ordered, but flexible structures called liquid crystals,” says Dr Bharat. “These form sheaths surrounding bacterial cells, acting like a ‘suit of armour’ and forming a barrier that help prevent antibiotics from reaching and killing the bacteria.”
Armed with this new knowledge of how Pf4 viruses are helping protect P. aeruginosa bacteria, the team then generated several candidate drugs to disrupt the formation of this liquid crystal shield.
“These potential new drugs could prove hugely beneficial for children with cystic fibrosis in the future,” says Dr Bharat. “Dismantling the Pf4 liquid crystal suit of armour protecting P. aeruginosa bacteria could help improve the effectiveness of existing antibiotics at clearing life-threatening chest infections.”
This research was completed on
Around 10,400 people in the UK – including over 4,000 children – are living with an inherited condition called cystic fibrosis.1 Sadly, two people will lose their lives to the disease every week.2 A major cause of illness and death is persistent chest infections with a bacterium called Pseudomonas aeruginosa. These form structures called biofilms that help them to avoid destruction by antibiotics and the immune system. Dr Tanmay Bharat is leading a team at the University of Oxford who are aiming to understand how biofilms help protect the bacteria and identify new ways to break them down. They hope this will lead to improved treatments that can help clear life-threatening infections from the airways of children with cystic fibrosis.
Action Medical Research and the Cystic Fibrosis Trust are jointly funding this research.
How are children’s lives affected now?
An estimated 1 in every 2,500 babies born in the UK has cystic fibrosis.3 Children experience a range of symptoms including a persistent cough, shortness of breath and frequent chest infections – caused by sticky mucus clogging their lungs and airways.
“Sadly, there is no cure for cystic fibrosis,” says Dr Bharat. “Medications or physiotherapy can help ease a child’s symptoms. But these can be time-consuming – sometimes taking as long as four hours every day – which can have a dramatic impact on their quality of life.”
Although life expectancy is improving for people with the condition, many will lose their lives too soon. Often this is due to progressive damage to their lungs caused by bacterial infections that are hard to treat.
“One bacterium, called Pseudomonas aeruginosa, is a particular problem for people with cystic fibrosis,” says Dr Bharat. “It forms a biofilm that coats the lining of their airways, acting as a barrier that stops antibiotics and immune cells from destroying the bacteria.”
How could this research help?
“If we could identify new ways to wipe out these bacteria by breaking down biofilms, it would help children with cystic fibrosis live longer, better lives,” says Dr Bharat.
The team are investigating substances made and released by the bacteria to understand how they help them to form biofilms that can ‘trap’ antibiotics making them less effective. They will also test specific small biological molecules to see if they can disrupt or prevent biofilms from forming, which they hope will improve the success of antibiotic treatment.
The World Health Organisation lists Pseudomonas aeruginosa as the highest priority for the development of new antibiotic treatments, so the results of this study could shed new light on how to beat it.
“Our work could open the door for enabling treatments to destroy these bacteria, helping children with cystic fibrosis overcome serious and potentially fatal infections,” says Dr Bharat.
References
- Cystic Fibrosis Trust. UK Cystic Fibrosis Registry. 2016 Annual Data Report. Published August 2017. https://www.cysticfibrosis.org.uk/the-work-we-do/uk-cf-registry/reporting-and-resources [Website accessed 28 November 2017]
- British Lung Foundation. Cystic Fibrosis statistics: https://statistics.blf.org.uk/cystic-fibrosis [Website accessed 28 November 2017]
- NHS Choices website: https://www.nhs.uk/conditions/cystic-fibrosis/ [website accessed 28 November 2017]
| Project Leader | Dr Tanmay A M Bharat, PhD |
| Project Team | Professor Christoph M Tang, PhDDr Rachel M Exley, PhDDr Abul K Tarafder PhD |
| Project Location | Sir William Dunn School of Pathology, University of Oxford |
| Project duration | 3 years |
| Date awarded | 21 November 2017 |
| Project start date | 15 January 2018 |
| Project end date | 14 January 2021 |
| Grant amount | £179,835 |
| Grant code | GN2634 |
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