Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms23095157
Keywords
Mycobacterium tuberculosis; lineage 2; Beijing; in vivo transcriptomics; murine model; RNAseq; virulence
Funding
- Ministerio de Ciencia, Tecnologia e Innovacion de Colombia -MINCIENCIAS [CT-731-2018]
- Consejo Nacional de Ciencia y Tecnologia-CONACyT, Mexico [CB-2013-223279]
- Universidad Nacional de Colombia, Facultad de Medicina, Proyecto Hermes [53688, 42665, 37136, 55935]
- MINCIENCIAS, Colombia [CT-80740-004-2020]
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This study analyzed the transcriptomic differences between Beijing-Like SIT-190 and Beijing-Classic SIT-1 isolates of Mycobacterium tuberculosis in a murine model of progressive tuberculosis. The results showed differential transcriptional programs between these two strains, with Beijing-Like SIT-190 being associated with host immune response and hypoxia, and Beijing-Classic SIT-1 being associated with proteolysis and protein folding.
Mycobacterium tuberculosis (MTB) lineage 2/Beijing is associated with high virulence and drug resistance worldwide. In Colombia, the Beijing genotype has circulated since 1997, predominantly on the pacific coast, with the Beijing-Like SIT-190 being 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. Bacterial 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 bacterial 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-resistant genotype.
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