# Genomic variations in Mycobacterium tuberculosis from the lungs and blood of HIV-infected individuals in Uganda: insights into compartmentalization

## TL;DR

This study explores genomic differences in tuberculosis bacteria from blood and lungs of HIV-positive patients in Uganda, finding that blood isolates have unique genetic variations linked to survival outside the lungs.

## Contribution

The study identifies 11 virulence genes with non-synonymous SNPs in MTB-blood isolates that may enhance their persistence outside the lungs.

## Key findings

- MTB-blood isolates have 11 virulence genes with distinctive non-synonymous SNPs linked to increased survival and tissue pathology.
- Most INDELs were found in non-virulence genes, with some shared between MTB-blood and -lung isolates.
- The findings suggest MTB-blood isolates have genomic adaptations that allow persistence outside the lungs.

## Abstract

Mycobacterium tuberculosis (MTB) clinical strains are relatively varied at the genome level. This in-silico study analyzed genomic differences between MTB isolates from the blood and lungs of TB-HIV positive cohorts in Uganda. The hypothesis was that isolates from the blood have distinct SNPs and INDELs that make them better survivors. Twenty-four MTB-blood and -lung sequences were aligned against the H37Rv reference genome and analyzed using BWA-MEM, IGV, SAMtools, FreeBayes, and SnpEff. Comparative analysis revealed that MTB-blood isolates had 11 virulence genes with distinctive non-synonymous SNPs involved in increasing colony-forming units, lowering host survival, enhancing tissue pathology, and allowing for human host persistence. The majority of INDELs were found in non-virulence genes, with the remainder in both MTB-blood and -lung sequences. The study suggests that MTB-blood isolates have distinctive SNPs that explain their capacity to persist outside of the lungs. However, further research is needed to understand the significance of these SNPs in the pathogenesis of MTB.

Mycobacterium tuberculosis (MTB) clinical strains have high genomic variability, and there is a knowledge gap on the genomic differences between MTB isolates from the blood and lungs of TB-HIV positive patients in Uganda. This study found that MTB-blood isolates had 11 virulence genes with distinctive non-synonymous SNPs that may contribute to their capacity to persist outside of the lungs. These findings provide insight into the genomic basis of MTB adaptation in different host environments, but further research is needed to fully understand the significance of these SNPs in MTB pathogenesis.