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Understanding nitrogen metabolism could revolutionize tuberculosis treatment

Understanding nitrogen metabolism could revolutionize TB treatment
Metabolic network showing carbon and nitrogen metabolism. Pathways of carbon and nitrogen metabolism include glycolysis (EMP), pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and anaplerotic reactions (ANA). Nitrogen source ammonium; carbon source glycerol. Reactions and metabolites involving nitrogen are shown in red. The inset (Appendix Fig S1 enlarged version) shows the last bifurcated step of the arginine biosynthesis, according to the genome-scale metabolic model sMTB2.0 (López-Agudelo et al, 2020). Citrulline is aminated either by free nitrogen to form arginine (arginine deiminase, ARCA), or aspartate is acting as nitrogen donor and arginine is formed via a two-step reaction with the intermediate argininosuccinate (argininosuccinate synthase (ARGG) and argininosuccinate lyase (ARGH)). Because the carbon backbone is the same for both branches, 13C labeling alone is not able to resolve the fluxes of either of these pathways. Credit: Molecular Systems Biology (2023). DOI: 10.15252/msb.202211099

Development of new drugs to effectively target the bacterium that causes tuberculosis (TB) could be one step closer following an important discovery from the University of Surrey.

The Surrey study used a technology called fluxomics to reveal important information about how cells process , which could help us better understand how harmful bacteria survive and cause disease. These findings have significant implications for studying the behavior and impact of pathogenic bacteria on human health.

In the most comprehensive study of its kind, the research team from Surrey conducted a study on the bacterium that causes tuberculosis, called Mycobacterium tuberculosis (Mtb). They wanted to understand how nitrogen is processed within Mtb cells, which is essential for the bacterium's survival. Surprisingly, previous studies had mostly examined the role of carbon in Mtb's survival, leaving the role of nitrogen poorly understood.

Dr. Khushboo Borah Slater, co-author of the study and research fellow from the University of Surrey, said, "Drug resistance is a major problem affecting tuberculosis treatment. New drugs are urgently needed to tackle the growing threat of this infectious disease and finding out more about how nitrogen is metabolized within cells could help us achieve this. Using drugs to target the nitrogen metabolism could be a novel way to disrupt how the bacterium survives, multiplies and spreads inside the human host cell."

Using the new fluxomic tool, Bayesian 13C15N-metabolic flux analysis, developed at Surrey and with Forschungszentrum Jülich, researchers were, for the first time, able to track both carbon and within Mtb cells. Following rigorous statistical assessment of all carbon and nitrogen within the bacterium, researchers were able to identify the crucial role the amino acid glutamate plays within the nitrogen metabolism in Mtb, providing the important target for new development.

Professor Johnjoe McFadden, co-author of the study from the University of Surrey, added, "Understanding the Mtb's nitrogen metabolism will help to develop drugs to tackle TB. Specifically creating drugs that target the amino acid glutamate could disrupt the nitrogen metabolism and curb the spread of the disease.

"The technology we developed will play a key role in learning more about the carbon and nitrogen metabolisms in any and could pave the way for more effective drug treatments being created for other human diseases."

This study was published in the journal Molecular Systems Biology and was conducted in partnership with Forschungszentrum Jülich, Germany.

More information: Khushboo Borah Slater et al, One‐shot 13 C 15 N ‐metabolic flux analysis for simultaneous quantification of carbon and nitrogen flux, Molecular Systems Biology (2023). DOI: 10.15252/msb.202211099

Journal information: Molecular Systems Biology

Citation: Understanding nitrogen metabolism could revolutionize tuberculosis treatment (2023, March 27) retrieved 18 July 2024 from https://phys.org/news/2023-03-nitrogen-metabolism-revolutionize-tuberculosis-treatment.html
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