Phylogenomic and clinical perspectives of an East Asia-specific cluster of Mycobacterium massiliense.

Abstract

Mycobacterium abscessus subspecies massiliense (MAM) can form genetically related clusters through continuous within-host adaptations. What is the epidemiological and clinical significance of the sequence type 120 (ST120) strain of MAM, an East Asia-specific cluster? and Methods: Isolates were obtained from patients with MAM pulmonary disease at Seoul National University Hospital between October 1, 2019, and December 31, 2023. These isolates were analyzed using multilocus sequence typing, colony morphotyping, and evaluated for glycopeptidolipid (GPL) biosynthesis-related gene deletions. Whole-genome sequencing was performed for phylogenomic and pangenome analyses, incorporating MAM genome data from public databases. Finally, the clinical course and treatment outcomes of patients infected with ST120 were evaluated. Among the isolates obtained from 136 patients, 50 (36.8%) were classified as ST120. All ST120 isolates exhibited a rough colony morphotype and harbored deletions in GPL biosynthesis-related genes. From 796 global strains, ST120 was exclusively identified in the isolates obtained from South Korea (51/137 isolates, 37.1%), Japan (3/53, 5.7%), and Taiwan (2/52, 3.8%). Genomic analysis revealed the stepwise genetic evolution of ST120, suggesting transmission from Taiwan to Japan, and Japan to South Korea. The ST120 strains exhibited genetic mutations associated with virulence and structural alterations within the ESX system. Consequently, patients with ST120 strain infections had a higher prevalence of cavitary disease (23/50, 46%) than those infected with non-ST120 strains (19/86, 22.1%; P=0.004). Among those who initiated treatment, the proportion of microbiological cure was lower in patients with ST120 infection (6/15, 40.0%) than in those with non-ST120 infection (24/34, 70.6%; P=0.043). ST120, a strain predominantly found in South Korea, is characterized by the extensive loss of GPL biosynthesis-related genes and is associated with increased disease severity and worse treatment outcomes.