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Mycobacterium tuberculosis strain:Beijing | isolate:M16

ABSTRACT: Mycobacterium tuberculosis strain:Beijing | isolate:M16 Genome sequencing and assembly

PROVIDER: PRJNA273400 | ENA |

REPOSITORIES: ENA

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Transcriptional profile of Beijing/East-Asian Mycobacterium tuberculosis isolates

Project description:Transcriptional profile comparison among Beijing and non-Beijing M. tuberculosis isolates. Three M. tuberculosis strains were compared. The laboratory reference strain, H37Rv, belongs to the Euro-American or lineage 4. Two clinical isolates of the East-Asian or lineage 2: 98_1663 is a pre-Beijing or Group 1 isolate, and HN878 is a Beijing or Group 5 isolate. Three replicates were performed for each comparison using two different biological samples.

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Project description: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.

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Project description:Tuberculosis continues as an important public health problem. Particularly considering Beijing-family strains of Mycobacterium tuberculosis, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several over-expressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Contrary, mice infected with BL displayed a profile which included the over-expression of several genes associated with immune- suppression, including Nkiras, Dleu2 and Sphk2, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis.

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