Genomic characterization and SNP analysis connect respiratory infections caused by Mycobacterium intracellulare with...

Non-tuberculous mycobacteria are emerging respiratory pathogens that can persist in treated water systems. In 2018, a cluster of Mycobacterium intracellulare lung infections was linked to a pool facility in Australia, prompting an epidemiological and genomic investigation. M. intracellulare was isolated from five sputum samples across four clinical cases and from fourteen pool water samples across a total of five collection time points. All cases were resolved following exclusion from the pool facility, with only one patient requiring short-term steroids; none of the patients required anti-mycobacterial treatment. To test if this was a point-source outbreak, whole-genome sequencing of mycobacteria recovered from patients and the pool was implemented. Initial analysis confirmed all patient and water isolates were M. intracellulare with sequence type 210. A complete, circular genome was constructed from one of the isolates linked to this cluster and was used as a reference genome for high-resolution core genome SNP analysis. This analysis showed tight clustering of M. intracellulare genomes from patient and pool water isolates that were distinct from other M. intracellulare. Thus, epidemiological and comparative genome analysis strongly implicated the pool as the origin of these infections.