Genomic Analysis of a Hospital-Associated Outbreak of Mycobacterium abscessus: Implications on Transmission.

Whole genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus (MABC). Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission. Existing genomic studies were limited by a lack of WGS from environmental MABC isolates. In this study, we retrospectively analyzed the core and accessory genomes of 26 M. abscessus subsp. abscessus (MAA) isolates collected over seven years. Clinical isolates (n=22) were obtained from a large hospital-associated outbreak of MAA, the outbreak hospital before or after the outbreak, a neighboring hospital, and two outside laboratories. Environmental MAA isolates (n=4) were obtained from outbreak hospital water outlets. Phylogenomic analysis of study isolates revealed three clades with pairwise genetic distances ranging from 0-135 single nucleotide polymorphisms (SNPs). Compared to a reference environmental outbreak isolate, all seven clinical outbreak isolates and the remaining three environmental isolates had highly similar core and accessory genomes, differing by up to 7 SNPs and a median of 1.6% accessory genes, respectively. Although genomic comparisons of 15 non-outbreak clinical isolates revealed greater heterogeneity, five (33%) isolates had fewer than 20 SNPs compared to the reference environmental isolate, including two unrelated outside laboratory isolates with less than 4% accessory genome variation. Detailed genomic comparisons confirmed environmental acquisition of outbreak isolates of MAA. SNP distances alone, however, did not clearly differentiate the mechanism of acquisition of outbreak versus non-outbreak isolates. We conclude that successful investigation of MAA clusters requires molecular and epidemiologic components, ideally complemented by environmental sampling.