Genomic Characterisation Reveals Within-Host Evolution of Mycobacterium avium Chronicity

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Summary of Genome Medicine, https://doi.org/10.1186/s13073-025-01549-y 
Dr. Aaron M. Walsh  et al.

Points

Researchers analyzed 287 Mycobacterium avium isolates from 56 patients over 10 years to characterize the within-host evolution of this chronic pathogen.
Genomic comparison of isolates from Ireland and two European cohorts confirmed the circulation of dominant M. avium clones internationally, clustering within a tight 13-SNP threshold.
The combined cohort analysis revealed that M. avium communities frequently acquired new strains and evolved over time within the microenvironment of individual hosts.
Evidence of positive selection was found in 13 distinct mycobacterial genes, suggesting genetic adaptation strategies that enhance the pathogen’s ability to persist.
Multiple virulence-associated genes under selection could confer resistance to host defense mechanisms and antibiotics, identifying novel targets for future therapeutic investigation.

Summary

This study employed Whole Genome Sequencing (WGS) to elucidate the persistent nature and within-host evolutionary dynamics of Mycobacterium avium, a major cause of chronic infection in vulnerable populations. The analysis encompassed 287 M. avium isolates, which were sampled longitudinally from 56 chronically infected patients. The dataset integrated 50 newly sequenced genomes from 20 patients in an Irish cohort, followed for up to 10 years, with 237 published genomes from 2 pre-existing European cohorts. This methodology permitted both a wide-context evaluation of the Irish strains and a combined, in-depth analysis of genomic changes occurring over the course of chronic infection across all 3 cohorts.

The genomic analysis confirmed existing observations regarding the international circulation of dominant clones, identifying 2 instances where Irish strains clustered with other European strains within a narrow 13-SNP threshold. Critically, across the three cohorts, the study consistently demonstrated that M. avium communities evolve over time within individual hosts, indicating that the acquisition of new strains is a frequent event during chronic infection. These findings underscore a dynamic process of genomic adaptation, with evidence of positive selection in 13 distinct mycobacterial genes, suggesting evolutionary pressure from the host environment.

The genes identified as being under positive selection included multiple virulence-associated genes, which potentially confer resistance to host defense mechanisms and current antibiotics. These WGS-derived insights into the within-host evolution of M. avium provide novel understanding of the pathogen’s strategies for persistence. The identified genetic targets offer critical avenues for therapeutic investigation aimed at disrupting the mechanisms of chronicity and developing more effective treatment strategies.

Link to the article: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-025-01549-y

References

Walsh, A. M., Roycroft, E., Hinchion, K., Basdeo, S. A., Sheedy, F. J., Crispie, F., Cotter, P. D., McLaughlin, A. M., Keane, J., Fitzgibbon, M. M., & Gleeson, L. E. (2025). Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution. Genome Medicine, 17(1), 120. https://doi.org/10.1186/s13073-025-01549-y