Use of murine model to study virulence of epidemically significant Mycobacterium tuberculosis genotypes and to evaluate effectiveness of chemotherapy
Abstract
The clinical manifestations of tuberculosis (TB) in humans represent a complex interaction between the causative agent, Mycobacterium tuberculosis, and the immune response of the human host. Using the murine model, we compared virulence of M. tuberculosis strains of the medically significant genotypes and evaluated the effectiveness of anti-TB therapy and inflammatory response in infected mice. The C57BL/6 mice were infected with multidrug-resistant clinical M. tuberculosis strains of Beijing and LAM genotypes. Control groups were not treated and experimental groups received adequate treatment with moxifloxacin, linezolid, bedaquiline and perchlozone. After 2 and 5.5 months of therapy, groups of mice were euthanized and studied for bacterial load, histology, lung pathology, and biochemical markers of liver damage. Whole genome sequencing was performed on all bacterial isolates from the lungs of the treated mice and the obtained fastq files were analyzed using SAM-TB tool and Geneious package. This study was funded by Russian Science Foundation (grant 24-44-00004). The anti-TB therapy reduced the inflammation and tuberculous lung damage in all groups of mice, even in those infected with the most virulent strain Beijing 396. A significant effect of the anti-TB therapy was observed at both time-point for all groups. The highest effectiveness of the therapy was observed in mice infected with the least virulent strains Beijing 6691 and LAM 7074. At the same time, in 3 out of 4…
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