Pioneering new analysis at University of Cambridge brings more effective treatments for Mycobacterium abscessus lung infections a step closer for people with CF

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Researchers at the University of Cambridge have applied new techniques and methods of scientific analysis to understand more about the serious lung infections in people with CF caused by Mycobacterium abscessus bacteria, part of the NTM group of infections. Their exciting findings have moved us a step closer to being able to treat this infection much more effectively.

The researchers are funded through the UK CF Innovation Hub, a partnership between Cystic Fibrosis Trust and the University of Cambridge. Their results were published in the prestigious scientific journal Nature Microbiology this week.

Why is this research needed?

People with CF are susceptible to hard-to-treat lung infections, that can be very disruptive to day to day life. The treatments for infections caused by the bacteria Mycobacterium abscessus (M. abscessus) are taken for a long time - they involve months of intravenous antibiotics treatment, followed by further oral or nebulized antibiotics for many more months. Not only is this a big treatment burden for people with CF, but the side effects of the treatments themselves can cause  nausea, stomach upsets and extreme tiredness.

Sometimes this extensive treatment regime is not effective at removing the infection, due to antimicrobial resistance (AMR). AMR is where medicines such as antibiotics stop working as infection-causing bugs adapt themselves to avoid the effects of the treatment. When treatments don’t work the infection can lead to inflammation and permanent lung damage. More research is urgently needed to develop new treatments for M. abscessus that can remove the infection more quickly with less side effects.

When I first got diagnosed with NTM, I was told that there was no ‘go-to’ treatment to tackle this bug. It was all a game of ‘trial and error’ and you may be lucky if the treatment worked and it got rid of the infection. But in most cases you were stuck with it. Now 13 years later I’m still growing it. Research in this area is so important as it could lead to new medicines that are better at getting rid of this infection for good, and giving those who have it a better quality of life

Sara, who is living with CF

Are all infections caused by M. abscessus the same?

There are many genetically different variants, or strains of the bacteria M. abscessus that are found in the lungs of people with CF. Some strains of M. abscessus are easily removed from the body and cause no infection. In comparison, other strains are harder to remove and cause lung infection.

When people develop M. abscessus lung infection, there is a lot of variation from person to person in how bad the infection is, how easy it is to treat and the effects on their overall health. This is due to the strain of M. abscessus they are infected with. But researchers don’t know how the genetic differences between these strains cause these variations. The results of the research published today has provided some answers to this question.

What did the researchers find?

Professor Andres Floto and colleagues at the UK CF Innovation Hub have looked at how the genetic changes cause the differences in people’s experience of M. abscessus infection. They have identified new ‘virulence factors’ that determine how aggressive an infection caused by the bacteria is, and have linked their results back to people with CF who were infected with specific strains. Their results have moved us a step closer to being able to treat M. abscessus infections much more effectively.

Unravelling how genes are working together

Scientists know that genes work together to make different parts of the bacteria function. This makes it much more difficult to unpick which genetic differences make a lung infection more aggressive, for example.

The team looked at the whole genetic profile of over 300 different strains of M. abscessus, and compared them to computer models of the proteins they produce. For each change in a gene, they looked at what that meant for how the corresponding protein worked. Then they looked at patterns of genetic changes in the same bacterial strain – this gave them clues as to which genes were working together. Finally, they confirmed their results using different methods and linked them back to the health of people with CF with specific strains of M. abscessus infection.

Photo of Professor Andres Floto “This is the first study to define the genetic changes in clinical strains of Mycobacterium abscessus that are responsible for increased virulence and worse health outcomes. This work builds on two previous research studies. We’ll use this knowledge to develop tests to predict the likely outcome of people infected with M. abscessus, and to create antibiotics against several of these newly discovered virulence factors,” commented Professor Andres Floto, Director of UK CF Innovation Hub.

“We are delighted that researchers within the UK CF Innovation Hub are being so successful in understanding more about how M. abscessus causes such serious infections in people with CF. We’re excited about how these results might be used to accelerate the development of new, more effective treatments,” said Dr Lucy Allen, Director of Research at the Trust.

The research was published in Nature Microbiology on 25 August 2022. Boeck, L., Burbaud, S., Skwark, M. et al. Mycobacterium abscessus pathogenesis identified by phenogenomic analyses. Nat Microbiol (2022). and a commentary on the paper in the same issue Comas, I., Moreno-Molina, M. Phenogenomics of Mycobacterium abscessusNat Microbiol (2022).

This work builds on previous research from the UK CF Innnovation Hub published in Science and Nature Microbiology in 2021.

We believe that the work by Boeck and colleagues heralds the dawn of a large-scale genotype–phenotype diversity mapping era in microbial genomics.

Comas & Moreno-Molina, Nature Microbiology commentary, August 2022

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