Yelamanchi, SD and Arun Kumar, ST and Mishra, A and Keshava Prasad, TS and Surolia, A (2022) Metabolite Dysregulation by Pranlukast in Mycobacterium tuberculosis. In: Molecules, 27 (5).
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Abstract
Mycobacterium tuberculosis has been infecting millions of people worldwide over the years, causing tuberculosis. Drugs targeting distinct cellular mechanisms including synthesis of the cell wall, lipids, proteins, and nucleic acids in Mtb are currently being used for the treatment of TB. Although extensive research is being carried out at the molecular level in the infected host and pathogen, the identification of suitable drug targets and drugs remains under explored. Pranlukast, an allosteric inhibitor of MtArgJ (Mtb ornithine acetyltransferase) has previously been shown to inhibit the survival and virulence of Mtb. The main objective of this study was to identify the altered metabolic pathways and biological processes associated with the differentially expressed metabolites by PRK in Mtb. Here in this study, metabolomics was carried out using an LC-MS/MSbased approach. Collectively, 50 metabolites were identified to be differentially expressed with a significant p-value through a global metabolomic approach using a high-resolution mass spectrometer. Metabolites downstream of argJ were downregulated in the arginine biosynthetic pathway following pranlukast treatment. Predicted human protein interactors of pranlukast-treated Mtb metabolome were identified in association with autophagy, inflammation, DNA repair, and other immune-related processes. Further metabolites including N-acetylglutamate, argininosuccinate, L-arginine, succinate, ergothioneine, and L-phenylalanine were validated by multiple reaction monitoring, a targeted mass spectrometry-based metabolomic approach. This study facilitates the understanding of pranlukastmediated metabolic changes in Mtb and holds the potential to identify novel therapeutic approaches using metabolic pathways in Mtb. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
| Item Type: | Journal Article |
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| Publication: | Molecules |
| Publisher: | MDPI |
| Additional Information: | The copyright for this article belongs to Authors |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 16 Mar 2022 06:09 |
| Last Modified: | 16 Mar 2022 06:09 |
| URI: | http://eprints.iisc.ac.in/id/eprint/71484 |
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