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

Borah, Khushboo, Girardi, Karina do Carmo de Vasconcelos, Mendum, Thomas A., Lery, Leticia Miranda Santos, Beste, Dany J.V., Lara, Flavio Alves, Pessolani, Maria Cristina Vidal, McFadden, Johnjoe and Boyle, Jon P. (2019) Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells mBio, 10 (6).

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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.

Item Type:	Article
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Borah, Khushboo k.borah@surrey.ac.uk Girardi, Karina do Carmo de Vasconcelos Mendum, Thomas A. T.Mendum@surrey.ac.uk Lery, Leticia Miranda Santos Beste, Dany J.V. D.Beste@surrey.ac.uk Lara, Flavio Alves Pessolani, Maria Cristina Vidal McFadden, Johnjoe J.Mcfadden@surrey.ac.uk Boyle, Jon P.
Date :	17 December 2019
Funders :	RCUK-CONFAP Research Partnership Call, BBSRC (Biotechnology and Biological Science Research Council), Medical Research Council (MRC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
DOI :	10.1128/mBio.02351-19
Copyright Disclaimer :	© 2019 Borah et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license
Contributors :	Contribution Name Email ORCID http://www.loc.gov/loc.terms/relators/EDT Boyle, Jon P.
Uncontrolled Keywords :	Mycobacterium leprae; Schwann cells; Glucose; Mycobacterium tuberculosis; Macrophage; Phosphoenolpyruvate carboxylase; Carbon metabolism
Depositing User :	Diane Maxfield
Date Deposited :	31 Jan 2020 16:39
Last Modified :	31 Jan 2020 16:40
URI:	http://epubs.surrey.ac.uk/id/eprint/853537

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