Close related Drug-Resistance Beijing isolates of Mycobacterium tuberculosis reveal a different transcriptomic signature in a murine disease progression model.

Mycobacterium tuberculosis (MTB) Beijing genotype is associated with high virulence and drug resistance worldwide. In Colombia, the Beijing genotype circulates since 1997 predominantly on the pacific coast, being the Beijing-Like SIT-190 more prevalent. This genotype conforms to a drug-resistant cluster and shows a fatal outcome in patients. To better understand virulence determinants, we performed a transcriptomic analysis with a Beijing-Like SIT-190 isolate (BL-323), and Beijing-Classic SIT-1 isolate (BC-391) in progressive tuberculosis (TB) murine model. RNA was extracted from mice lungs on days 3, 14, 28, and 60. On average, 0.6% of the total reads mapped against MTB genomes and of those, 90% against coding genes. The strains were independently associated as determined by hierarchical cluster and multidimensional scaling analysis. Gene ontology showed that in strain BL-323 enriched functions were related to host immune response and hypoxia, while proteolysis and protein folding were enriched in the BC-391 strain. Altogether, our results suggested a differential transcriptional program when evaluating these two closely related strains. The data presented here could potentially impact the control of this emerging, highly virulent and drug resistance genotype. We used Balb/c Mice infected with two close related Mycobacterium tuberculosis Beijing Strains. Afther the infection kinetics we obtained the whole trancriptome of the M. tuberculosis at early, middle and late infection stage to se the whole expression profile of the bacteria in the animal experimental model directrly from lungs