Understanding Mtb's nitrogen metabolism could pave the way for more effective TB treatments

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 nitrogen, 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.

The study was conducted in partnership with Forschungszentrum Jülich, Germany.

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 nitrogen atoms within Mtb cells. Following rigorous statistical assessment of all carbon and nitrogen biochemical reactions 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 drug development.

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 living organisms and could pave the way for more effective drug treatments being created for other human diseases."

Johnjoe McFadden, Co-Author, Professor, University of Surrey

This study was published in the journal Molecular Systems Biology.

Source:
Journal reference:

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

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