Mapping of IS6110 insertion sites in Mycobacterium bovis isolates in relation to adaptation from the animal to human host.

The physiological role and impact of IS6110 insertions on the biology of Mycobacterium tuberculosis complex is not well understood. Insertion of IS6110 in coding regions can cause loss of gene activity, while homologous recombination between two copies of IS6110 can result in the deletion of genes or in rearrangement of genomic regions involved. In addition to these genomic changes, IS6110 can also activate flanking genes through acting as a mobile promoter. In order to determine the possible role of IS6110 transposition in the adaptation to humans, we selected Mycobacterium bovis isolates from endogenous reactivation cases in elderly people in The Netherlands. The human isolates contained higher number of IS6110 copies in comparison to the bovine M. bovis strains. These additional integration sites of IS6110 were sequenced and analyzed. From 12 of such IS6110 insertion sites, 6 loci were located in the intergenic regions, and 6 other occurred within coding regions. IS6110 was inserted in a position where it might serve as a promoter in two cases. We conclude that IS6110 transpositions in M. bovis may be a driving force in the adaptation from the animal to the human host.