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Title: GarA is an essential regulator of metabolism in Mycobacterium tuberculosis
Authors: Ventura, Marcello
Rieck, Barbara
Boldrin, Francesca
Degiacomi, Giulia
Bellinzoni, Marco
Barilone, Nathalie
Alzaidi, Faisal
Alzari, Pedro M.
Manganelli, Riccardo
O'Hare, Helen M.
First Published: 21-Aug-2013
Publisher: Wiley-Blackwell
Citation: Molecular Microbiology, 2013, 90 (2), pp. 356-366
Abstract: Alpha-ketoglutarate is a key metabolic intermediate at the crossroads of carbon and nitrogen metabolism, whose fate is tightly regulated. In mycobacteria the protein GarA regulates the tricarboxylic acid cycle and glutamate synthesis by direct binding and regulation of three enzymes that use α-ketoglutarate. GarA, in turn, is thought to be regulated via phosphorylation by protein kinase G and other kinases. We have investigated the requirement for GarA for metabolic regulation during growth in vitro and in macrophages. GarA was found to be essential to Mycobacterium tuberculosis, but dispensable in non-pathogenic Mycobacterium smegmatis. Disruption of garA caused a distinctive, nutrient-dependent phenotype, fitting with its proposed role in regulating glutamate metabolism. The data underline the importance of the TCA cycle and the balance with glutamate synthesis in M. tuberculosis and reveal vulnerability to disruption of these pathways.
DOI Link: 10.1111/mmi.12368
ISSN: 0950-382X
eISSN: 1365-2958
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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