Whole transcriptome profiling is now almost routinely used in various fields of
biology, including microbiology. In vivo transcriptome studies
usually provide relevant information about the biological processes in the
organism and thus are indispensable for the formulation of hypotheses, testing,
and correcting. In this study, we describe the results of genome-wide
transcriptional profiling of the major human bacterial pathogen M.
tuberculosis during its persistence in lungs. Two
mouse strains differing in their susceptibility to tuberculosis were used for
experimental infection with M. tuberculosis. Mycobacterial
transcriptomes obtained from the infected tissues of the mice at two different
time points were analyzed by deep sequencing and compared. It was hypothesized
that the changes in the M. tuberculosis transcriptome may
attest to the activation of the metabolism of lipids and amino acids,
transition to anaerobic respiration, and increased expression of the factors
modulating the immune response. A total of 209 genes were determined whose
expression increased with disease progression in both host strains (commonly
upregulated genes, CUG). Among them, the genes related to the functional
categories of lipid metabolism, cell wall, and cell processes are of great
interest. It was assumed that the products of these genes are involved in
M. tuberculosis adaptation to the host immune system defense,
thus being potential targets for drug development.
We performed a comparative analysis ofMycobacterium aviumtranscriptomes (strain 724R) in infected mice of two different strains- resistant and susceptible to infection. Sets of mycobacterial genes transcribed in lung tissue were defined, and differentially transcribed genes were revealed. Our results indicate thatM. aviumgenes coding for enzymes of the Krebs cycle, oxidative phosphorylation, NO reduction, fatty acid biosynthesis, replication, translation, and genome modification are expressed at high levels in the lungs of genetically susceptible mice. The expression of genes responsible for cell wall properties, anaerobic nitrate respiration, fatty acid degradation, synthesis of polycyclic fatty acid derivatives, and biosynthesis of mycobactin and other polyketides is increased in the resistant mice. In the resistant host environment,Mycobacterium aviumapparently transitions to a latent state caused by the deficiency in divalent cations and characterised by anaerobic respiration, degradation of fatty acids, and modification of cell wall properties.
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