Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> 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 Mycobacterium leprae remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied 13C isotopomer analysis to measure carbon metabolism of M. lep...

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Autores principales:	Khushboo Borah, Karina do Carmo de Vasconcelos Girardi, Tom A. Mendum, Leticia Miranda Santos Lery, Dany J. V. Beste, Flavio Alves Lara, Maria Cristina Vidal Pessolani, Johnjoe McFadden
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Mycobacterium leprae Schwann cells glucose Mycobacterium tuberculosis macrophage phosphoenolpyruvate carboxylase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fef48e6de36f4127b20229e6a93e3109
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spelling	oai:doaj.org-article:fef48e6de36f4127b20229e6a93e31092021-11-15T15:54:47ZIntracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells10.1128/mBio.02351-192150-7511https://doaj.org/article/fef48e6de36f4127b20229e6a93e31092019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02351-19https://doaj.org/toc/2150-7511ABSTRACT New approaches are needed to control leprosy, but understanding of the biology of the causative agent Mycobacterium leprae remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied 13C isotopomer analysis to measure carbon metabolism of M. leprae in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, Mycobacterium tuberculosis, growing in its primary host cell, the macrophage. Using 13C isotopomer analysis with glucose as the tracer, we show that whereas M. tuberculosis imports most of its amino acids directly from the host macrophage, M. leprae 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 M. leprae, identifying this enzyme as a potential antileprosy drug target. IMPORTANCE 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 M. leprae while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, M. tuberculosis, replicating in macrophages. Our analysis revealed that unlike M. tuberculosis, M. leprae 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 M. leprae. Our findings provide the first metabolic signature of M. leprae in the host Schwann cell and identify novel avenues for the development of antileprosy drugs.Khushboo BorahKarina do Carmo de Vasconcelos GirardiTom A. MendumLeticia Miranda Santos LeryDany J. V. BesteFlavio Alves LaraMaria Cristina Vidal PessolaniJohnjoe McFaddenAmerican Society for MicrobiologyarticleMycobacterium lepraeSchwann cellsglucoseMycobacterium tuberculosismacrophagephosphoenolpyruvate carboxylaseMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium leprae Schwann cells glucose Mycobacterium tuberculosis macrophage phosphoenolpyruvate carboxylase Microbiology QR1-502
spellingShingle	Mycobacterium leprae Schwann cells glucose Mycobacterium tuberculosis macrophage phosphoenolpyruvate carboxylase Microbiology QR1-502 Khushboo Borah Karina do Carmo de Vasconcelos Girardi Tom A. Mendum Leticia Miranda Santos Lery Dany J. V. Beste Flavio Alves Lara Maria Cristina Vidal Pessolani Johnjoe McFadden Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
description	ABSTRACT New approaches are needed to control leprosy, but understanding of the biology of the causative agent Mycobacterium leprae remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied 13C isotopomer analysis to measure carbon metabolism of M. leprae in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, Mycobacterium tuberculosis, growing in its primary host cell, the macrophage. Using 13C isotopomer analysis with glucose as the tracer, we show that whereas M. tuberculosis imports most of its amino acids directly from the host macrophage, M. leprae 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 M. leprae, identifying this enzyme as a potential antileprosy drug target. IMPORTANCE 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 M. leprae while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, M. tuberculosis, replicating in macrophages. Our analysis revealed that unlike M. tuberculosis, M. leprae 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 M. leprae. Our findings provide the first metabolic signature of M. leprae in the host Schwann cell and identify novel avenues for the development of antileprosy drugs.
format	article
author	Khushboo Borah Karina do Carmo de Vasconcelos Girardi Tom A. Mendum Leticia Miranda Santos Lery Dany J. V. Beste Flavio Alves Lara Maria Cristina Vidal Pessolani Johnjoe McFadden
author_facet	Khushboo Borah Karina do Carmo de Vasconcelos Girardi Tom A. Mendum Leticia Miranda Santos Lery Dany J. V. Beste Flavio Alves Lara Maria Cristina Vidal Pessolani Johnjoe McFadden
author_sort	Khushboo Borah
title	Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_short	Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_full	Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_fullStr	Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_full_unstemmed	Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_sort	intracellular <named-content content-type="genus-species">mycobacterium leprae</named-content> utilizes host glucose as a carbon source in schwann cells
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/fef48e6de36f4127b20229e6a93e3109
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Intracellular <named-content content-type="genus-species">Mycobacterium leprae</named-content> Utilizes Host Glucose as a Carbon Source in Schwann Cells

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