top of page


In vitro host gene expression profiles in cross-infections of Mycobacterium tuberculosis ecotypes

P Ruiz-Rodriguez(1) M Caballer-Gual(1) G santamaria(1) H Hiza(1) J Galvis-Jimenez(1) M Coscolla(1)

1:Institute for integrative systems biology

Pathogen-host interaction is a complex interface where the compatibility between both organisms plays a major role determining the fate of the encounter. Mycobacterium tuberculosis is a clonal bacteria with very low genetic diversity, but infecting a great diversity of hosts. The relative impact of the different drivers of this bacteria-host compatibility are nor well understood. Here we aim to better understand molecular mechanisms associated with the differences in compatibility by comparing transcriptomic profiles of different bacteria and cell combinations in vitro.

We compared one strain from Lineage A4, typical of cattle infections, and Lineage A1 (the chimpanzee bacillus) with the two closest human lineages Lineage L5 and Lineage L6, infecting human and cattle cellular lines (THP-1 and BoMac). We categorized the infection outcomes as high compatibility (L5 with THP-1 and A4 with BoMac), low compatibility (L5 with BoMac and A4 with THP-1), and intermediate or unknown compatibility (L6 with both THP-1 and BoMac, and A1 with both THP-1 and BoMac). Our analysis identified upregulated and downregulated genes across the pairwise groups, finding synergies of strain-host infections and infection progression. One of our major findings was the identification of upregulated functions involved in intracellular containment of the bacteria and immune evasion in low compatibility combinations. Conversely, we observed functions related to cell replication affecting DNA of the host upregulated in high compatibility combinations. Our approach aims to elucidate molecular determinants of lineage-host preferences and contribute to a better understanding of tuberculosis pathogenesis.

bottom of page