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GarA is an essential regulator of metabolism in M ycobacterium tuberculosis
Author(s) -
Ventura Marcello,
Rieck Barbara,
Boldrin Francesca,
Degiacomi Giulia,
Bellinzoni Marco,
Barilone Nathalie,
Alzaidi Faisal,
Alzari Pedro M.,
Manganelli Riccardo,
O'Hare Helen M.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12368
Subject(s) - biology , kinase , metabolism , citric acid cycle , biochemistry , phosphorylation , mycobacterium smegmatis , microbiology and biotechnology , mycobacterium tuberculosis , tuberculosis , medicine , pathology
Summary 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 M ycobacterium tuberculosis , but dispensable in non‐pathogenic M ycobacterium 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.