New Insights Into Chronic Lung Infection Reveal Bacterial Evolution Over Time

Researchers have discovered how the bacterium Mycobacterium avium, a primary source of persistent lung infections, adapts and changes within patients during long-term illness. This recent study, conducted by teams from the Trinity Translational Medicine Institute and the Irish Mycobacterial Reference Laboratory, provides a clearer understanding of why this infection is so challenging to treat and why it frequently returns after therapy.

Chronic lung infections caused by M. avium are increasingly prevalent across the globe. Patients diagnosed with this condition often require prolonged antibiotic regimens, sometimes lasting a year or longer. Despite intensive treatment, only about half of patients experience successful outcomes, and relapses are common. The research team sought to address the reasons behind the bacterium's resilience and recurring nature.

To examine how M. avium evolves inside the body, scientists performed whole-genome sequencing on nearly 300 bacterial samples collected from patients in Ireland, the United Kingdom, and Germany. Twenty of these patients were treated at St James's Hospital in Ireland. By analyzing the bacterial DNA from samples taken over several years, the study tracked genetic changes and adaptations that occur during the course of infection.

The investigation revealed that persistent infection is typically not due to a single bacterial strain remaining in the lungs. Instead, many patients experience repeated reinfections with new strains, some of which are closely related to those found in other European countries. This suggests that environmental reservoirs may play a crucial role in continued transmission and reinfection.

• Frequent Reinfection: Patients often acquire new bacterial strains over time, indicating that reinfection from environmental sources is more common than relapse from a previous infection.
• Genetic Connections Across Borders: Bacterial strains in Irish patients were found to be genetically similar to those in the UK and Germany, highlighting potential cross-border environmental sources or shared exposure risks.
• Key Genes Under Pressure: Thirteen genes within M. avium showed significant adaptation, helping the bacterium withstand antibiotics, low oxygen environments, and immune system attacks.
• Antibiotic Resistance Evolution: Genetic changes associated with resistance to commonly used antibiotics, such as rifampicin, were noted in patients undergoing treatment, demonstrating the bacterium's ability to adapt under therapeutic pressure.

This study is the first to use whole-genome sequencing to monitor the evolution of M. avium within patients over extended periods. The findings indicate that the bacterium acquires new genetic mutations at a rate of about one change per year and that certain genes not previously linked to survival in the human body are crucial for adaptation. These genes are involved in managing oxidative stress and forming biofilms, both of which contribute to the bacterium's persistence.

The identification of specific genes under selective pressure offers new potential targets for the development of more effective therapies. Understanding the mechanisms that enable M. avium to survive antibiotic treatment and immune responses is essential to improving patient outcomes and reducing relapse rates.

Researchers plan to further investigate the function of these thirteen key genes in laboratory settings. Future studies will also employ advanced sequencing methods to detect genetic changes not captured by current technologies and analyze environmental samples to determine the sources of reinfections. Expanding the research to additional patient groups will help confirm whether these patterns are consistent across different populations.

This study enhances the understanding of how chronic lung infections persist and evolve, providing valuable insights for clinicians and researchers working to combat these challenging diseases.