Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis

Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, a...

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Autores principales: Jansen, Robert S., Mandyoli, Lungelo, Hughes, Ryan, Wakabayashi, Shoko, Pinkham, Jessica T., Selbach, Bruna, Guinn, Kristine M., Rubin, Eric J., Sacchettini, James C., Rhee, Kyu Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181641/
https://www.ncbi.nlm.nih.gov/pubmed/32327655
http://dx.doi.org/10.1038/s41467-020-15876-8
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author Jansen, Robert S.
Mandyoli, Lungelo
Hughes, Ryan
Wakabayashi, Shoko
Pinkham, Jessica T.
Selbach, Bruna
Guinn, Kristine M.
Rubin, Eric J.
Sacchettini, James C.
Rhee, Kyu Y.
author_facet Jansen, Robert S.
Mandyoli, Lungelo
Hughes, Ryan
Wakabayashi, Shoko
Pinkham, Jessica T.
Selbach, Bruna
Guinn, Kristine M.
Rubin, Eric J.
Sacchettini, James C.
Rhee, Kyu Y.
author_sort Jansen, Robert S.
collection PubMed
description Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.
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spelling pubmed-71816412020-04-29 Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis Jansen, Robert S. Mandyoli, Lungelo Hughes, Ryan Wakabayashi, Shoko Pinkham, Jessica T. Selbach, Bruna Guinn, Kristine M. Rubin, Eric J. Sacchettini, James C. Rhee, Kyu Y. Nat Commun Article Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis. Nature Publishing Group UK 2020-04-23 /pmc/articles/PMC7181641/ /pubmed/32327655 http://dx.doi.org/10.1038/s41467-020-15876-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jansen, Robert S.
Mandyoli, Lungelo
Hughes, Ryan
Wakabayashi, Shoko
Pinkham, Jessica T.
Selbach, Bruna
Guinn, Kristine M.
Rubin, Eric J.
Sacchettini, James C.
Rhee, Kyu Y.
Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title_full Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title_fullStr Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title_full_unstemmed Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title_short Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis
title_sort aspartate aminotransferase rv3722c governs aspartate-dependent nitrogen metabolism in mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181641/
https://www.ncbi.nlm.nih.gov/pubmed/32327655
http://dx.doi.org/10.1038/s41467-020-15876-8
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