Unique genomic sequences in a novelMycobacterium aviumsubsp.hominissuislineage enable fine scale transmission route tracing during pig movement

Abstract

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial (NTM) disease in human and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig and human MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. We conducted a variable number of tandem repeat (VNTR), genome phylogenetic tree analysis, historical recombination analysis and genome content analysis. Consistent with the results of previous studies, VNTR revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human. Recombination analysis indicated that most pig isolates could be classified into SC2/4 and SC3. To our surprise, four isolates belonged to a new lineage in the global MAH population. Members of this group had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. As the members of this new lineage were rare, we were able to trace the putative transmission route via their host pigs. Together, these results reveal the diversity in the pig MAH population and clarify the difference of source of infection and the vector of transmission between humans and pigs.