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AbstractIntroduction Mycobacterium avium lung disease (MA-LD) poses significant challenges in predicting disease progression. This study aimed to characterize the genomic diversification of M. avium and define its relationship to disease progression. Methods We investigated the whole-genome sequence data of 36 M. avium clinical strains. Comparative analyses of genomic structure and sequence were undertaken between subjects with progressive disease (PD) and those with stable disease (SD). Results M. avium strains were classified into two types: type A and type nonA, according to the 1.4-Mb genomic inversion. All type A strains (n = 15) were isolated from PD subjects, and type nonA strains were referred to as type B and type C strains and were isolated from PD subjects (n = 10) and SD subjects (n = 11), respectively. The three strain types (A/B/C) were mainly distributed in distinct clusters of the amino acid identity-based phylogenetic tree. We further identified the specific set of single-nucleotide variations discriminating between type B and type C strains. The three M. avium genotypes were associated with disease progression in an independent validation cohort of 32 subjects. Conclusions The genomic types of M. avium may represent a valuable biomarker for estimating the risk for MA-LD progression.
Tanaka et al. (Fri,) studied this question.