P056

1:Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal; 2:Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, Lisboa, Portugal; 3:Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

Non-Tuberculous Mycobacteria (NTM) is estimated to be responsible for over 280 000 deaths worldwide and 9.9 million disability-adjusted life years. Within this group, Mycobacterium avium comprises a diverse opportunistic pathogen, frequently associated with pulmonary/extrapulmonary disease, whose genetic diversity and population structure remain insufficiently understood.

This study aimed to characterize the phylogeny and population structure of M. avium from diverse geographies. Using large-scale genomics combined with associated metadata for M. avium isolates, publicly available data were retrieved and subjected to quality control, reference and de novo assembly, mapping and variant calling. Genome-wide phylogenetic reconstruction enabled population structure analysis, cluster identification and analysis of the phylogenetic dispersion of resistance associated variants.

The study includes 2917 genomes from 22 countries, comprising human (n=871), animal (n=1270) and environmental (n=90) isolates. Four main lineages were identified, three of which composed exclusively of M. avium subsp. hominissuis (MAH) and a fourth that included MAH, M. avium subsp. avium and M. avium subsp. paratuberculosis isolates. Sublineages were mostly clustered by geographic location and host. A total of 261 possible transmission clusters were identified (<20 SNPs), most within the same country. Clustering across distinct sources highlight possible transmission between reservoirs. Resistance associated mutations were identified in 169 isolates: rrs A1408G (n=58) and rrl A2058/A2059 (n=111). These mutations were exclusively found in human MAH isolates and reflect a continued emergence of resistance to aminoglycosides and macrolides, respectively.

These findings highlight the global reach and diversification of M. avium along with cross-reservoir transmission and clade-specific proclivity for resistance development.