Mycobacterium tuberculosis carbon and nitrogen metabolic fluxes

Abstract

Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens causing tuberculosis (TB), a devastating infectious disease responsible for the highest human mortality and morbidity. The emergence of drug resistant strains of the pathogen has increased the burden of TB tremendously and new therapeutics to overcome the problem of drug resistance are urgently needed. Metabolism of Mtb and its interactions with the host is important for its survival and virulence; this is an important topic of research where there is growing interest in developing new therapies and drugs that target these interactions and metabolism of the pathogen during infection. Mtb adapts its metabolism in its intracellular niche and acquires multiple nutrient sources from the host cell. Carbon metabolic pathways and fluxes of Mtb has been extensively researched for over a decade and is well-defined. Recently, there has been investigations and efforts to measure metabolism of nitrogen, which is another important nutrient for Mtb during infection. This review discusses our current understanding of the central carbon and nitrogen metabolism, and metabolic fluxes that are important for the survival of the TB pathogen.

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“…The same applies to several pathways related to the regulation of the metabolism, such as the GO terms "Tricarboxylic acid cycle" (TCA) and "Glycolysis/ gluconeogenesis", which were commonly represented in both species, but again being represented by different proteins. Our findings support a central role for these terms in the metabolism, model proposed by Xu et al (2022) for M. tuberculosis, since amino acids, such as arginine, are synthesized from TCA using carbon metabolites from glycolysis as an energy source, which support the significant role of these pathways in TB in bovine and porcine. Interestingly, and in conjunction with these previous GO terms, "Nitrogen metabolism" was another term activated in cattle, involving proteins such as carbonic hydrogenase-like proteins (CA12 and CA2) and carbamoyl phosphate synthase-1 (CPS-1), which has been shown to play a relevant role in mycobacterial nutrition and survival (44).…”

Proteomic analysis of granulomas from cattle and pigs naturally infected with Mycobacterium tuberculosis complex by MALDI imaging

“…(2022) for M. tuberculosis , since amino acids, such as arginine, are synthesized from TCA using carbon metabolites from glycolysis as an energy source, which support the significant role of these pathways in TB in bovine and porcine. Interestingly, and in conjunction with these previous GO terms, “Nitrogen metabolism” was another term activated in cattle, involving proteins such as carbonic hydrogenase-like proteins (CA12 and CA2) and carbamoyl phosphate synthase-1 (CPS-1), which has been shown to play a relevant role in mycobacterial nutrition and survival ( 44 ).…”

Biomarker discovery for tuberculosis using metabolomics

“…These reviews have different focuses, with each one covering part of the studies in the literature. While some covered relatively broad aspects of TB research ( Goletti et al, 2016 ; Goletti et al, 2018 ; Kumar et al, 2017 ; du Preez et al, 2019 ; Kontsevaya et al, 2021 ), others addressed more focused topics, such as diagnostic biomarker ( Haas et al, 2016 ; du Preez et al, 2017 ), treatment monitoring ( Luies et al, 2017a ; Pitaloka et al, 2022 ), drug discovery ( Jansen and Rhee, 2017 ; Tuyiringire et al, 2018 ; Goff et al, 2020 ; Xu and Borah, 2022 ), mechanism of action of drugs ( Awasthi and Freundlich, 2017 ; Yuan et al, 2021 ) or anti-TB compounds ( Sakallioglu et al, 2021 ), drug resistance of Mtb and drug toxicty ( Combrink et al, 2020 ), as well as HIV/TB co-infection ( Liebenberg et al, 2021 ). Besides pulmonary TB, there are reviews on the status of metabolomics studies on tuberculosis meningitis as well ( Zhang et al, 2018 ; Isaiah et al, 2020 ; Huynh et al, 2022 ).…”