Researchers found that Mycobacterium avium acquires roughly one new genetic change per year, with thirteen specific genes showing signs of adaptation to antibiotics
A bacterium causing difficult-to-treat lung infections can evolve in real time in the lung, with re-infection common, a new Irish study has found.
Researchers at Trinity Translational Medicine Institute (TTMI) and the Irish Mycobacterial Reference Laboratory at St James's Hospital have uncovered how the bacterium Mycobacterium avium (M. avium) - a leading cause of chronic lung infections - changes and adapts inside patients over many years of illness.
Their findings could help doctors understand why M. avium infections come back and why antibiotics sometimes fail.
"Our study shows that M. avium can evolve in real time inside the lung," said Dr Aaron Walsh, lead author on the study and TTMI researcher.
"Understanding which genes help it survive may point us towards new treatment targets for this increasingly common and stubborn infection."
M. avium causes a type of chronic lung infection that's becoming more common around the world. Treating M. avium lung disease is challenging, with patients often needing 12 months or more of several antibiotics. Despite this, treatment still fails in up to half of cases and many patients get sick again even after therapy.
The research team used whole-genome sequencing to analyse nearly 300 bacterial samples from patients in Ireland, the UK and Germany, including 20 Irish patients treated at St James's Hospital. By reading the DNA of these bacteria over time, the scientists tracked how M. avium evolves, swaps strains and develops resistance while living in the human lung.
They found that infection is often not caused by one single long-term strain, but by repeated reinfection with new ones.
Many patients picked up new strains over time, suggesting they were reinfected from the environment rather than suffering relapse of the same infection. Some Irish strains were also found to be genetically almost the same as ones from UK and Germany.
The bacterium acquires roughly one new genetic change per year, and the study found that thirteen specific genes showed signs of adaptation to antibiotics, immune attack and low-oxygen stress.
Researchers also saw changes in a gene linked to rifampicin resistance in two patients receiving that drug, suggesting that resistance can appear during treatment.
"Some of those genes weren't previously linked to survival of M. avium inside the body," said Dr Emma Roycroft, specialist medical scientist in the Irish Mycobacterial Reference Laboratory.
"For example, one involved in handling oxidative stress and another in forming biofilms. This has highlighted important pathways that could be targeted with new treatments. It was also striking that Irish, British and German samples were so closely related, even though the patients had never met."
The research team now plans to test in the lab how the 13 genes they identified help M. avium survive. They will also study environmental samples to find where reinfections come from and hope to expand their research to other patient groups to see if the same patterns occur.