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Intracellular Mycobacterium tuberculosis Exploits Multiple Host Nitrogen Sources during Growth in Human Macrophages

Borah, Khushboo, Beyß, Martin, Theorell, Axel, Wu, Huihai, Basu, Piyali, Mendum, Tom A., Nӧh, Katharina, Beste, Dany J.V. and McFadden, Johnjoe (2019) Intracellular Mycobacterium tuberculosis Exploits Multiple Host Nitrogen Sources during Growth in Human Macrophages Cell Reports, 29 (11). 3580-3591.e4.

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Abstract

Nitrogen metabolism of Mycobacterium tuberculosis(Mtb) is crucial for the survival of this important pathogen in its primary human host cell, the macrophage, but little is known about the source(s) and their assimilation within this intracellular niche. Here, we have developed 15N-flux spectral ratio analysis(15N-FSRA) to explore Mtb’s nitrogen metabolism; we demonstrate that intracellular Mtb has access to multiple amino acids in the macrophage, including glutamate, glutamine, aspartate, alanine, glycine,and valine; and we identify glutamine as the pre-dominant nitrogen donor. Each nitrogen source is uniquely assimilated into specific amino acid pools,indicating compartmentalized metabolism during intracellular growth. We have discovered that serine is not available to intracellular Mtb, and we show that a serine auxotroph is attenuated in macrophages. This work provides a systems-based tool for exploring the nitrogen metabolism of intracellular pathogens and highlights the enzyme phosphoserine transaminase as an attractive target for the development of novel anti-tuberculosis therapies.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Borah, Khushbook.borah@surrey.ac.uk
Beyß, Martin
Theorell, Axel
Wu, HuihaiH.Wu@surrey.ac.uk
Basu, Piyali
Mendum, Tom A.T.Mendum@surrey.ac.uk
Nӧh, Katharina
Beste, Dany J.V.D.Beste@surrey.ac.uk
McFadden, JohnjoeJ.Mcfadden@surrey.ac.uk
Date : 10 December 2019
Funders : Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council
DOI : 10.1016/j.celrep.2019.11.037
Copyright Disclaimer : Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Depositing User : Diane Maxfield
Date Deposited : 31 Jan 2020 17:02
Last Modified : 31 Jan 2020 17:04
URI: http://epubs.surrey.ac.uk/id/eprint/853538

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