How Mycobacterium abscessus infections are passed on: Putting the pieces together

People with CF are susceptible to developing infections, due to the thick sticky mucus in their lungs. The infections can be extremely difficult to treat, where many bugs are resistant to the antimicrobial medicines available. Left untreated the infections may cause progressive lung damage and shorten people’s lives.

The Trust is funding research both to develop new medicines to treat the infections and also to prevent people with CF from becoming infected with these bugs. New research published today in Nature Microbiology has found a missing piece in understanding how people become infected with particular variants of the bacteria Mycobacterium abscessus (M. abscessus), that cause serious and hard-to-treat infections in people with cystic fibrosis.

Dr Lucy Allen, Director of Research at the Trust said “This study is an important advance in our understanding of how infection-causing variants of M abscessus are passed on. Lung infections caused by this bacteria are a serious concern for people with cystic fibrosis. Antibiotics treatments for this infection can last for more than a year, cause unpleasant side effects and can be very disruptive to daily life. We’re delighted that our investment in the UK CF Innovation Hub is continuing to accelerate progress in this area.”

What is the background to this research?

Professor Julian Parkhill, Professor Andres Floto and colleagues within the UK CF Innovation Hub at Cambridge University – a multi disciplinary team including both lab and clinical researchers - have shown that specific infection-causing variants of M. abscessus can be passed on from person to person with cystic fibrosis. Before this, doctors and researchers thought that the infection was picked up from the environment.

In earlier research, the scientists found that the infection could be passed person to person by analysing the DNA of the bacteria in patient samples, and by comparing when patients had visited the clinic. They did this by comparing the DNA of M. abscessus within samples from people with CF from clinics in USA, Australia and the UK. If the DNA was a very close match, it meant that the same variant of the bacterium had been transmitted between two different people.

However, they found very closely matching samples from people with CF in different countries, people who had never met, and people who had never been to the same clinic.

Crucially, the research study published today may explain how these variants transmitted between people with CF around the world who do not have direct links.

How did a CF infection-causing variant of M abscessus travel around the world?

To look for clues to solving this puzzle Professors Floto and Parkhill studied the genetics of the infection-causing variants in more detail. They used two different methods.

 The first thing they did was to work out when these M. abscessus variants started to spread amongst people. The research team did this by tracing backwards through the genetic changes that had occurred in the bacteria, a bit like working out a family tree. They found that some variants of M. abscessus expanded rapidly in the 1970s. This rapid expansion coincided with a time when people with CF started to survive longer, and be treated together in CF centres, suggesting this may have contributed to these expansions. However, the family trees also suggested that the earliest emergence of these M. abscessus variants pre-dated this time.

A link with smoking?

Each time a bacterial strain is exposed to a new local environment or stress, it leaves a trail of DNA changes (mutations). The mutations that occur in each new environment are unique and these changes are known as a ‘genetic signature’. The genetic signature is a record of what has happened to the bacteria many years ago. Professor Parkhill and Floto analysed the genetic signatures of M. abscessus variants to understand how they first emerged and then travelled around the world.

Although M. abscessus infection is mainly reported in people with CF, doctors have found that people with smoking-related lung damage are also susceptible to M. abscessus infections. The research team thought that this might explain the appearance and long-distance transmission of the infection-causing M. abscessus variants. To find out, they looked at the mutations that occur in M. abscessus to see if the cigarette smoke had left a specific ‘genetic signature’ within the DNA of the bacteria.

When the research team in Cambridge looked at the M. abscessus genetic signatures in samples from people with CF around the world, they indeed found the presence of a genetic signature from cigarette smoke.

This suggests that smokers who don’t have CF may have allowed the appearance of these variants, and subsequently acted as a carrier of M. abscessus between people with cystic fibrosis. The team confirmed this by showing the patterns of how the bacteria were passed on (known as ‘transmission networks’) built from the bacterium’s family tree.

“Our analysis is the first time these genetic signatures have been used in bacteria to study their past environmental exposures. It allowed us to demonstrate a connection between M. abscessus infection in smokers and people with CF, but we need much more research to find out how frequent that connection is and its effect on people with cystic fibrosis. We don’t know how often smokers would pass on the infection to people with CF - we haven’t yet designed the experiment to test this out” explained Professor Parkhill.

Professor Andres Floto said “This research tells us more about how people with CF pick up serious and hard to treat M. abscessus infections. However, further studies are needed to understand how infected smokers could be involved. Until then people with CF and their clinical teams should continue with their existing strict guidelines to avoid cross infection.”

The full details of this research paper are as follows: Ruis, C., Bryant, J.M., Bell, S.C. et al. Dissemination of Mycobacterium abscessus via global transmission networks. Nature Microbiology (2021). https://doi.org/10.1038/s41564-021-00963

 Cystic fibrosis (CF) is a genetic condition which causes sticky mucus to build up in the lungs and digestive system. It affects more than 10,600 people in the UK. One in 25 of us carries the faulty gene that causes it, usually without knowing.

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