Diversity and antimicrobial resistance profiles of Mycobacterium avium complex clinical isolates in Thailand based on whole genome comparative analysis

Abstract

The Mycobacterium avium complex (MAC) is a group of closely related nontuberculous mycobacteria that can cause various diseases in humans. In this study, genome sequencing, comprehensive genomic analysis, and antimicrobial susceptibility testing of 66 MAC clinical isolates from King Chulalongkorn Memorial Hospital, Bangkok, Thailand were carried out. Whole-genome average nucleotide identity (ANI) revealed the MAC species distribution, comprising 54 (81.8%) M. intracellulare, 6 (9.1%) M. avium, 5 (7.6%) M. colombiense, and 1 (1.5%) M. timonense. Phylogenetic analysis revealed a high diversity of M. intracellulare isolates and their evolutionary relationships which could be divided into 2 subspecies: M. intracellulare subsp. intracellulare and M. intracellulare subsp. chimaera. In addition, M. intracellulare subsp. chimaera mostly clustered in the distinct clades separated from M. intracellulare strains originating from other countries. Most MAC isolates were resistant to linezolid and moxifloxacin based on phenotypic antimicrobial susceptibility testing. Mutations within rrl gene associated with clarithromycin resistance were detected in M. intracellulare and M. colombiense. The pan-genome analysis presented clade-specific proteins for M. intracellulare, such as PE and PPE protein families. This study provides valuable insights into the genomic diversity and antimicrobial resistance profiles of MAC isolates circulating in Thailand, which are useful for clinical management, guiding the development of targeted diagnostic, and treatment strategies for MAC infections.