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.

Highlights

  • Despite decades of research and development in vaccination and therapeutics, tuberculosis (TB) still remains one of the world’s deadliest infectious diseases [1]

  • This study demonstrated that like carbon co-catabolism, Mycobacterium tuberculosis (Mtb) can co-assimilate two amino acids as nitrogen sources in vitro

  • Recent decades of research have advanced our understanding of Mtb’s metabolic physiology and identified cellular processes and components that are essential for its virulence and survival in the host

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Summary

Mycobacterium tuberculosis carbon and nitrogen metabolic fluxes

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. 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.

Introduction
Glycolytic and gluconeogenic carbon metabolism
Anaplerotic node and the TCA cycle fluxes
Methyl citrate cycle fluxes for lipid metabolism
Nitrogen metabolic fluxes
Participation in metabolism
Conclusions and future perspectives
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