Changes in the metabolism of Mycobacterium tuberculosis during the course of TB treatment

According to the WHO, tuberculosis morbidity remains high, despite a trend towards stabilization the situation remains extremely tense due to the distribution of resistant forms. The aim of the present study was to use omics approaches to detect changes in M. tuberculosis strains during anti-tuberculosis (TB) therapy In this work we used three serial clinical isolates of M. tuberculosis Beijing B0/W148 cluster from one patient with pulmonary tuberculosis. Strains were obtained before (strain I- 2008 year), during (strain II-2009 year) and after (strain III-2012 year) TB therapy. The susceptibility testing was done using the BACTEC MGIT 960 system. WGS and transcriptome analysis were conducted on Illumina HiSeq 2500. Proteome analysis was performed on a Q Exactive HF. According to the DST results initial strain I was pre-XDR, while both strain II and strain III were XDR. Strain II was resistant to high concentrations of isoniazid, and strain III was additionally resistant to ofloxacin. According to WGS these strains revealed mutations in the GyrA (D94A) and inhA promoter (t-8c) associated with the drug resistance. The effects of inhA t-8a mutation was observed on the proteomic and transcriptomic levels. Comparative quantitative proteome analysis revealed an increased representation of proteins coded by the mce1 gene of the operon in strains II and III. Increased representation of relevant proteins under the influence of TB therapy may indicate a favor of bacterial adaptation to drugs. Also our results demonstrated increased representation of the FAS-II system proteins (HtdX, HtdY) in strains obtained after therapy.