Horizontal Gene Transfer

One of the major virulence traits of M. tuberculosis is its ability to parasitize host macrophages. Pools of mutants generated by STM have also been used in vitro, in THP-1 macrophage-like cells, to search for genes involved in macrophage parasitism. We have identified 23 mutants corresponding to 21 genes or genetic regions that were attenuated in their ability to survive and multiply inside human macrophages. Mutants disrupted in the ABC transporter-encoding genes Rv0986 and Rv0987 were further characterized as being impaired in their ability to bind to host cells.

From Rosas-Magallanes V. et al. Mol Biol Evol. 2006 23:1129-35

The Rv0986-Rv0987-Rv0988 operon is highly homologous to ate-H in Agrobacterium tumefaciens, an a-proteobacteria infecting plant roots. This led us to suggest that the operon might have been acquired by the bacilli through horizontal gene transfer (HGT). Using a combination of molecular biology and in silico approaches we have shown that this operon is indeed specific to the M. tuberculosis complex and has been acquired by the ancestor of the complex through HGT from a γ-proteobacterium species. Further analysis of the M. tuberculosis genome using genomic signature revealed 48 M. tuberculosis-specific chromosomal regions with atypical characteristics, potentially due to HGT from environmental bacteria. Many display features typical of the genomic islands found in other bacteria, including residual material from mobile genetic elements, flanking direct repeats, insertion in the vicinity of tRNA sequences, and genes with putative or documented virulence functions. Genetic diversity in these regions is being investigated in a collection of clinical isolates representative of the M. tuberculosis species. The function of some of these genomic islands in mycobacterial virulence is being investigated in in vitro and in vivo models.

Potential origin of genomic islands