**Metabolic Changes of** *Mycobacterium tuberculosis* **during the Anti-Tuberculosis Therapy**

**Julia Bespyatykh 1,\*, Egor Shitikov 1,\*, Dmitry Bespiatykh 1 Andrei Guliaev 1, Ksenia Klimina 1, Vladimir Veselovsky 1, Georgij Arapidi 1,2, Marine Dogonadze 3, Viacheslav Zhuravlev 3, Elena Ilina 1 and Vadim Govorun 1**


Received: 24 January 2020; Accepted: 15 February 2020; Published: 18 February 2020

**Abstract:** Tuberculosis, caused by *Mycobacterium tuberculosis* complex bacteria, remains one of the most pressing health problems. Despite the general trend towards reduction of the disease incidence rate, the situation remains extremely tense due to the distribution of the resistant forms. Most often, these strains emerge through the intra-host microevolution of the pathogen during treatment failure. In the present study, the focus was on three serial clinical isolates of *Mycobacterium tuberculosis* Beijing B0/W148 cluster from one patient with pulmonary tuberculosis, to evaluate their changes in metabolism during anti-tuberculosis therapy. Using whole genome sequencing (WGS), 9 polymorphisms were determined, which occurred in a stepwise or transient manner during treatment and were linked to the resistance (GyrA D94A; *inhA* t-8a) or virulence. The effect of the *inhA* t-8a mutation was confirmed on both proteomic and transcriptomic levels. Additionally, the amount of RpsL protein, which is a target of anti-tuberculosis drugs, was reduced. At the systemic level, profound changes in metabolism, linked to the evolution of the pathogen in the host and the effects of therapy, were documented. An overabundance of the FAS-II system proteins (HtdX, HtdY) and expression changes in the virulence factors have been observed at the RNA and protein levels.

**Keywords:** omics analysis; TB treatment; system analysis; Beijing B0/W148
