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Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells.

Abstract

New approaches are needed to control leprosy, but understanding of the biology of the causative agent remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied C isotopomer analysis to measure carbon metabolism of in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, , growing in its primary host cell, the macrophage. Using C isotopomer analysis with glucose as the tracer, we show that whereas imports most of its amino acids directly from the host macrophage, utilizes host glucose pools as the carbon source to biosynthesize the majority of its amino acids. Our analysis highlights the anaplerotic enzyme phosphoenolpyruvate carboxylase required for this intracellular diet of , identifying this enzyme as a potential antileprosy drug target. Leprosy remains a major problem in the world today, particularly affecting the poorest and most disadvantaged sections of society in the least developed countries of the world. The long-term aim of research is to develop new treatments and vaccines, and these aims are currently hampered by our inability to grow the pathogen in axenic culture. In this study, we probed the metabolism of while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, , replicating in macrophages. Our analysis revealed that unlike , utilized host glucose as a carbon source and that it biosynthesized its own amino acids, rather than importing them from its host cell. We demonstrated that the enzyme phosphoenolpyruvate carboxylase plays a crucial role in glucose catabolism in Our findings provide the first metabolic signature of in the host Schwann cell and identify novel avenues for the development of antileprosy drugs.

More information

Type
Journal Article
Author
Borah K
Girardi K
Mendum T
Lery L
Beste D
Lara F
Pessolani MC V
McFadden J

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