ArticlePLoS pathogens2017
PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Structural Modification of Indole Derivatives as PknB Inhibitors for Enhanced Enzymatic Inhibition and Antimycobacterial Activity.ACS omega · 2026Article
- Serine/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress.PLoS genetics · 2026Article
- Intracellular glutamine fluctuates with nitrogen availability and regulatesJournal of bacteriology · 2025Article
- A Phosphoproteomic Analysis of Mycobacterial PknG-Mediated Host Immune Evasion.Journal of proteome research · 2025Article
- Engineering the TCA cycle regulator GarA to increase erythromycin production inMicrobiology (Reading, England) · 2025Article
- Characterization of the Biological Effect Mediated by Mycobacterial Kinase PknG on Protein Phosphorylation and Acetylation.ACS omega · 2025Article
- Protein kinase G-a key regulator of pathogenesis in Mycobacterium tuberculosis infection.Archives of microbiology · 2025Review
- Proteomic characterization ofmSystems · 2025Article
- An atlas of bacterial serine-threonine kinases reveals functional diversity and key distinctions from eukaryotic kinases.Science signaling · 2025Article
- Genome-wide high-throughput transposon mutagenesis unveils key factors for acidic pH adaptation ofMicrobiology (Reading, England) · 2025Article
- S-nitrosylation-triggered secretion of mycobacterial PknG leads to phosphorylation of SODD to prevent apoptosis of infected macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Combating Tuberculosis via Restoring the Host Immune Capacity by TargetingInternational journal of molecular sciences · 2024Review
- A Novel Bi-Directional Channel for Nutrient Uptake across Mycobacterial Outer Envelope.Microorganisms · 2024Article
- Article
- Mycobacterium tuberculosis SecA2-dependent activation of host Rig-I/MAVs signaling is not conserved in Mycobacterium marinum.PloS one · 2024Article
- Mycobacterium smegmatis: The Vanguard of Mycobacterial Research.Journal of bacteriology · 2023Review
- Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials.Frontiers in microbiology · 2023Review
- Bacterial effector kinases and strategies to identify their target host substrates.Frontiers in microbiology · 2023Review
- The Repertoire of Solute-Binding Proteins of Model Bacteria Reveals Large Differences in Number, Type, and Ligand Range.Microbiology spectrum · 2022Article
- Article
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Abstract
Sensing and response to changes in nutrient availability are essential for the lifestyle of environmental and pathogenic bacteria. Serine/threonine protein kinase G (PknG) is required for virulence of the human pathogen Mycobacterium tuberculosis, and its putative substrate GarA regulates the tricarboxylic acid cycle in M. tuberculosis and other Actinobacteria by protein-protein binding. We sought to understand the stimuli that lead to phosphorylation of GarA, and the roles of this regulatory system in pathogenic and non-pathogenic bacteria. We discovered that M. tuberculosis lacking garA was severely attenuated in mice and macrophages and furthermore that GarA lacking phosphorylation sites failed to restore the growth of garA deficient M. tuberculosis in macrophages. Additionally we examined the impact of genetic disruption of pknG or garA upon protein phosphorylation, nutrient utilization and the intracellular metabolome. We found that phosphorylation of GarA requires PknG and depends on nutrient availability, with glutamate and aspartate being the main stimuli. Disruption of pknG or garA caused opposing effects on metabolism: a defect in glutamate catabolism or depletion of intracellular glutamate, respectively. Strikingly, disruption of the phosphorylation sites of GarA was sufficient to recapitulate defects caused by pknG deletion. The results suggest that GarA is a cellular target of PknG and the metabolomics data demonstrate that the function of this signaling system is in metabolic regulation. This function in amino acid homeostasis is conserved amongst the Actinobacteria and provides an example of the close relationship between metabolism and virulence.
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