**4. Conclusions**

This is a first report of the system omics analysis of *M. tuberculosis* Beijing B0/W148 cluster strains isolated from one patient at different stages of TB therapy. A clear correlation between genetic and phenotypic resistance to the antibiotics was demonstrated, documenting changes in the lipid metabolism, and production of virulence factors on the proteomic and transcriptomic levels. These changes imply that the anti-tuberculosis therapy play a crucial role in the regulation of bacterial biochemical pathways.

We show that integrating various approaches can advance our knowledge of the role and significance of microevolution in *M. tuberculosis* infection.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-0817/9/2/131/s1. Table S1: Variable SNPs among tree clinical isolates. Table S2: List of identified and quantified transcripts for RUS\_B0, 3955 and 2093 strains. Table S3: Proteins and peptides identified in RUS\_B0, 3955 and 2093 strains. Table S4: Quantitative proteomic analysis of RUS\_B0, 3955 and 2093 strains.

**Author Contributions:** Conceptualization, J.B. and E.S.; methodology, J.B., E.S., K.K., M.D. and V.V.; software, D.B., A.G., and G.A.; formal analysis, D.B., A.G., G.A., K.K., M.D. and V.V.; investigation, J.B., E.S.; resources, V.Z., E.I. and V.G.; data curation, J.B., E.S. and V.Z.; writing – original draft preparation, J.B. and E.S.; writing – review & editing, J.B, E.S. and D.B.; supervision, E.I.; project administration, V.G.; funding acquisition, J.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by Russian Foundation for Basic Research (project 18-34-00168).

**Acknowledgments:** We acknowledge the IBMC "Human Proteome" Core Facility for assistance with the generation of mass spectrometry data. We thank the Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency for providing the WGS platform.

**Conflicts of Interest:** The authors declare no conflict of interest.
