Using artificial sputum to understand CF lung infections

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New research, co-funded by Cystic Fibrosis Trust, has uncovered evidence that might explain why long-term infections, which are commonly experienced by people with cystic fibrosis (CF), are so difficult to treat.

The bacteria Pseudomonas aeruginosa (P. aeruginosa) causes harmful and difficult to treat lung infections in people with CF. Antibiotics often fail to clear these infections and researchers at the University of Cambridge have uncovered new evidence that may explain why.

Specific antibiotics are given to target different infection-causing bugs in the lungs of people with CF. However, there are many other types of bacteria, viruses and fungi present there too. While these bugs may not be directly causing harm, they can help bugs evade treatment and build up antimicrobial resistance.

A new way to model infection

Researchers at the University of Cambridge led by Professor Martin Welch have used ‘artificial sputum’ to model human airways. The team grew a mixture of bugs together, including Pseudomonas aeruginosa (P. aeruginosa), mirroring conditions in the airways more accurately. They then used this model to investigate how effective antimicrobial treatments were in this environment, and found that much higher doses of medicines than previously thought are needed to clear the infections.

For example, the team discovered how P. aeruginosa may evade colistin, a drug usually given to people with CF after other treatments have failed. They found that this newly discovered mechanism of resistance is already happening in those with CF.

The team’s findings may help explain why antimicrobials often fail to clear chronic infections. The researchers hope their findings will lead to greater understanding of how antimicrobials could be better used to treat lung infections in the future, which could make a big difference to the CF community.

“New treatments for CF lung infections are urgently needed. Professor Welch’s group have used a newly developed technology to understand more about the effects of antimicrobials such as antibiotics, on three important bugs that cause CF lung infections and are often found together in the lungs of people with CF.

“These results help to explain why antimicrobial treatments can fail to treat infections and this method of modelling the airways using artificial sputum, containing a mixture of bugs may provide a new way to test the effectiveness of new antimicrobial medicines.”

Dr Paula Sommer, Head of Research at Cystic Fibrosis Trust

Read more about this research in a press release from University of Cambridge

This research was published in the ISME journal: O’Brien, T. et al: ‘Decreased efficacy of antimicrobial agents in a polymicrobial environment.’ The ISME Journal, March 2022. DOI: 10.1038/s41396-022-01218-7

Cystic fibrosis (CF) is a genetic condition which causes sticky mucus to build up in the lungs and digestive system. It affects more than 10,800 people in the UK. One in 25 of us carries the faulty gene that causes it, usually without knowing.

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