Population structure of Mycobacterium avium subsp. hominissuis provides new insights into genomic evolution

<i>Mycobacterium avium</i> subsp. <i>hominissuis</i> (MAH) is a clinically important species of non-tuberculous mycobacteria that causes infections in a variety of hosts. This opportunistic pathogen is widespread in the environment, including natural and engineered water systems across the globe. To examine the current genetic diversity of this organism, we analysed 702 MAH genomes isolated from humans, pigs and environmental sources across six countries and three continents. Through Bayesian population structure analysis, we identified ten distinct global lineages, including seven previously described and three new ones. Several lineages exhibited regional clustering, including sequence cluster 6 (SC6) in Germany and SC8 in both the USA and Germany. Further analysis identified recombination hotspots in membrane proteins associated with virulence, antimicrobial resistance and immune modulation, driven by insertion sequences and other elements that frequently integrate at tRNA gene sites. This work demonstrates the remarkable genomic diversity of MAH and provides insight into the evolutionary mechanisms that contribute to its success as a pathogen in both humans and animals.