SRA

Background: Mycobacterium avium complex lung disease (MAC LD) is an increasing problem and difficult to treat.Methods: We performed whole genome sequencing of 95 longitudinal isolates from 35 patients with MAC LD.Results: Isolates fell into four phylogenetic clusters: M. intracellulare, M. avium, M. chimaera, and a fourth cluster. Isolates with predominantly M. intracellulare reads were particularly heterogeneous, with only 71%-96% M. intracellulare reads, and containing a mixture of other species. Surprisingly, in examining patients' longitudinal isolates, we noted that many patients (16/35 = 46%) switched species/clusters over time. Moreover, this phenomena was consistent, appearing in patients that experienced relapse, those that were on therapy, and those off of therapy (50%, 55%, and 38% of each patient group, respectively). Switching was robust to alternate bioinformatic approaches and was supported by antibiogram data.Conclusion: These data suggest that MAC LD, particularly with M. intracellulare, is a dynamic and often polymicrobial infection. The clinical significance of individual MAC species or mixtures of species requires further study.