Whole-genome phylogenetic analysis of Mycobacterium avium complex from clinical respiratory samples

The Mycobacterium avium complex (MAC) is a common causative agent causing nontuberculous mycobacterial (NTM) pulmonary disease worldwide. Whole-genome sequencing was performed on a total of 203 retrospective MAC isolates from respiratory specimens. Phylogenomic analysis identified eight subspecies and species. M. avium subspecies hominissuis (MAH) was the overwhelmingly dominant species (148/203, 72.9%). The other seven identified species were M. intracellulare subsp. yongonense (18/203, 8.9%), M. intracellulare subsp. chimaera (10/203, 4.9%), M. colombiense (11/203, 5.4%), M. paraintracellulare (6/203, 3%), M. marseillense (5/203, 2.5%), M. intracellulare (3/203, 1.5%), and M. avium subspecies paratuberculosis (2/203, 1%). Significant genetic clustering was observed among MAH isolates. Notably, a large cluster (<12 SNPs) of 76 MAH isolates bearing the same sequence type was observed. The presence of closely related isolates within hospital settings raises concerns about transmission routes with environmental sources potentially playing a significant role. Based on susceptibility breakpoints that are available for clarithromycin, amikacin, linezolid, and moxifloxacin, low rates of clarithromycin (0.5%, 1/203) and amikacin (1.5%, 3/203) phenotypic resistance were observed. While linezolid and moxifloxacin resistance were 25.6% (52/2030) and 46.3% (94/203), respectively. Drug resistance-associated loci were searched for mutations linked to phenotypic drug resistance. Of the entire cohort, only one isolate was found to have a A2059G 23S rRNA (rrl) gene mutation responsible for macrolide resistance.