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The prominent transcriptional and metabolites changes of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin B1

ABSTRACT: Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing and LC/MS. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation. LC/MS indicated that most of amino acids and ADP decreased in VB1 processed culture. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro. This study will be benefit for our deeply understanding for impact of VB1 to M.tuberculosis.

ORGANISM(S): Mycobacterium tuberculosis variant bovis

PROVIDER: GSE114949 | GEO | 2019/05/08

REPOSITORIES: GEO

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The prominent transcriptional changes of Mycobacterium bovis BCG str. Tokyo 172 following induction by vitamin B1

Project description:Vitamin B1 (VB1) is a key dietary nutrient and crucial cofactor, which exhibits a series of regulatory functions on cellular processes and the activation of the immune system. To date, the precise effect of VB1 on Mycobacterium tuberculosis has not been fully described. In the present study, the direct influence of VB1 treatment on M. bovis BCG was determined using RNA-sequencing. The selection of this strain was used due to its common physiological features with M.tuberculosis. The investigation of the M. bovis BCG transcription demonstrated significant changes in certain metabolic and cellular process such as the decrease in fatty acid, cholesterol and glycolipid catabolism, the decrease in DNA replication and protein translation, the reduction in cell division and cell wall formation and the induction of arginine biosynthesis. In addition, growth assays indicated that VB1 inhibited the BCG growth rate in vitro, whereas LC/MS analysis demonstrated that the concentration of arginine was higher following VB1 supplementation. It is suggested that VB1 could be used for the treatment of tuberculosis potentially.

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Project description:Vitamins are organic compounds and essential nutrients required by host organism. Recent studies have shown that vitamin B1(VB1) and vitamin C (Vc) could inhibit Mycobacterium tuberculosis growth. However, the precise role of VB1 and Vc in M.tuberculosis are still not well understand. Therefore, in this study, the transcriptional, metabolic and methylation profiles of VB1 and VC treated Mycobacterium. bovis BCG were analyzed by RNA-sequencing, LC-MS (Liquid chromatography coupled to mass spectrometry) and SMRT. The RNA-seq show that gene encoding cysteine synthase A was significantly up-regulated under both vitamins treatment, metabolic study show that most of amino acids decreased in VB1 treated BCG, in constrast, most of amino acids increased in VC treated samples. Methylome data show that m4c modificatiion partically is present in VC treated BCG and the expression of most genes harboring m4c methylation modificaiton increased. In all, these data imply that potentially increased concentration of cysteine might lead to BCG growth inhibition induced by VB1 and VC duing to produce superoxide which could cause DNA damage via Fetions reacition. The m4c methylation modification could promote gene transcription to some extent. In all, this study will benefit for us to futher understand the roles of VB1 and VC which could be used as potential anti-tuberculosis drugs.

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Project description:BACKGROUND:Vitamin B1 (VB1) is a crucial dietary nutrient and essential cofactor for several key enzymes in the regulation of cellular and metabolic processes, and more importantly in the activation of immune system. To date, the precise role of VB1 in Mycobacterium tuberculosis remains to be fully understood. RESULTS:In this study, the transcriptional and metabolic profiles of VB1-treated Mycobacterium. bovis BCG were analyzed by RNA-sequencing and LC-MS (Liquid chromatography coupled to mass spectrometry). The selection of BCG strain was based on its common physiological features shared with M. tuberculosis. The results of cell growth assays demonstrated that VB1 inhibited the BCG growth rate in vitro. Transcriptomic analysis revealed that the expression levels of genes related to fatty acid metabolism, cholesterol metabolism, glycolipid catabolism, DNA replication, protein translation, cell division and cell wall formation were significantly downregulated in M. bovis BCG treated with VB1. In addition, the metabolomics LC-MS data indicated that most of the amino acids and adenosine diphosphate (ADP) were decreased in M. bovis BCG strain after VB1 treatment. CONCLUSIONS:This study provides the molecular and metabolic bases to understand the impacts of VB1 on M.bovis BCG.

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