Researchers discover how Mycobacterium abscessus evolves

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Trust-funded researchers within our UK CF Innovation Hub partnership have published their work in the journal ‘Science’ about how M. abscessus is evolving in the lungs of people with CF to become more virulent, suggesting that changes may need to be made in the way this infection is managed.

Mycobacterium abscessus causes an aggressive lung infection in people with CF and is extremely difficult to treat; it can take over a year of strong antibiotic treatments to clear, with damaging and unpleasant side effects, due to the bacteria’s resistance to antibiotic treatments.

That is why in 2017 the CF community identified treatments and eradication of this infection was highlighted as among the top 10 health priorities.

The team at the UK CF Innovation Hub, a partnership co-funded by the Cystic Fibrosis Trust and the University of Cambridge, has been studying the genetic evolution of M. abscessus to understand how it is transmitted and better ways to treat it.

About bacterial evolution

Bacteria are constantly evolving, by continuously changing their DNA. Each DNA change, or mutation, is random, like rolling a dice. The change might give the bacteria an advantage or a disadvantage, depending on their environment. Evolutionary changes in DNA can make bacterial infections more difficult to treat.

Studying how the DNA of infection-causing bacteria changes over time can give researchers important information about how people become infected. They can also highlight which genes within the bacteria’s DNA are important in causing more aggressive forms of infection.

Professors Andres Floto and Julian Parkhill and their colleagues at the University of Cambridge studied the evolution of M. abscessus in people with CF by analysing 1,173 sputum samples from a total of 526 people with cystic fibrosis. Samples were obtained from those attending clinics in the UK, as well as other parts of Europe, the USA and Australia.

What did the researchers find?

By studying several samples from the same person, the researchers were able to analyse samples from different parts of their lungs. Each M. abscessus bacteria that found its way to a different part of the lungs will have evolved separately.

Using mathematical models, the team was able to trace the genetic ‘family tree’ of each bacterial sample collected. Professor Andres Floto, explained their findings: “What you end up with is parallel evolution in different parts of an individual’s lung. This offers bacteria the opportunity for multiple rolls of the dice until they find the most successful mutations. The net result is a very effective way of generating different adaptations to the host and increasing its ability to cause lung damage.

“This suggests that you might need to treat the infection as soon as it is identified. At the moment, because the drugs can cause unpleasant side effects and have to be administered over a long period of time – often as long as 18 months – doctors usually wait to see if the bacteria is definitely causing illness before treating the infection. But what this does is give the bug plenty of time to evolve repeatedly, potentially making it more difficult to treat.”

Professor Julian Parkhill, added: “M. abscessus can be a very challenging infection to treat and can be very dangerous to people living with cystic fibrosis, but we hope insights from our research will help us reduce the risk of transmission, stop the bug evolving further, and potentially prevent the emergence of new disease-causing mutations.”

Dr Lucy Allen, the Trust’s Director of Research, said: “This exciting research brings real hope of better ways to treat lung infections that are resistant to other drugs. Our co-funded UK CF Innovation Hub with the University of Cambridge really shows the power of bringing together world-leading expertise to tackle a health priority identified by people with cystic fibrosis. We’re expecting to see further impressive results in the future coming from our joint partnership.

“After I was first infected with M  abscesses in 2003 I spent four months in hospital and since then have had several long stays. Spending huge swathes of time in hospital results in disrupted lives and time lost. And, months of arduous IV antibiotics with very unpleasant side effects, can also lead to longer term medical issues. I remain hopeful that new ways of treating this terrible and exhausting infection are on their way, and the exciting news today is one step towards that” said Luke who has CF and has lived with M. abscessus infection for many years.

You can read more about this research on the University of Cambridge’s website and in their Science paper (Bryant JM et al. Stepwise pathogenic evolution of Mycobacterium abscessus. Science; 30 Apr 2021).

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