Genomic insights into persistent infections, reinfections, and subspecies diversity of Mycobacteroides abscessus: A whole-genome sequencing study of Thai and global isolates.

Mycobacteroides abscessus is a highly resistant pathogen with significant genetic diversity and complicating clinical management. This study used whole-genome sequencing to analyze genomic variations in seven serially collected isolates from three Thai patients, distinguishing between persistent infections and reinfections. Comparative analysis with 43 global isolates revealed subspecies-specific genetic diversity and distribution patterns. Among Thai isolates, two paired samples (P7.1-P7.2 and P15.1-P15.2) were persistent infections (same clone), while two (P8.1-P8.2 and P15.2-P15.3) were reinfections (different clones). Genome-wide comparisons revealed depth distribution patterns and gene cluster variations among different clones, whereas minimal divergence was observed within persistent infections. Although initial pan-genome analysis identified unique genes in same-clone pairs (P7.1 vs. P7.2 and P15.1 vs. P15.2), further validation using raw read mapping confirmed these genes were not truly unique. Analysis of global isolates showed subspecies-specific genetic variations. M. abscessus subsp. abscessus (MAB) and M. abscessus subsp. massiliense (MMAS) exhibited distinct genotypically drug resistance profiles, with unique core genes linked to adaptation and resistance mechanisms. STRING analysis identified 42 unique core genes in MAB, with 11 gene interactions-truB, prmC_2, and aguA_2 showing the highest interaction scores. In contrast, MMAS had 11 unique core genes with a single interaction between lgrD_4 and rnc. Subsequent validation using NCBI BLAST showed only fmt_2 and aguA_2 were truly unique to MAB. This study provides new insights into the genomic evolution of M. abscessus during persistent and reinfections and genetic variation among subspecies. The findings enhance understanding of M. abscessus epidemiology and may inform therapeutic and infection control.