Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like conditions

Khan, Mehak Zahoor ; Bhaskar, Ashima ; Upadhyay, Sandeep ; Kumari, Pooja ; Rajmani, Raju S. ; Jain, Preeti ; Singh, Amit ; Kumar, Dhiraj ; Bhavesh, Neel Sarovar ; Nandicoori, Vinay Kumar (2017) Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like conditions Journal of Biological Chemistry, 292 (39). pp. 16093-16108. ISSN 0021-9258

Full text not available from this repository.

Official URL:

Related URL:


Protein kinase G (PknG), a thioredoxin-fold–containing eukaryotic-like serine/threonine protein kinase, is a virulence factor in Mycobacterium tuberculosis, required for inhibition of phagolysosomal fusion. Here, we unraveled novel functional facets of PknG during latency-like conditions. We found that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient-limited conditions, suggesting its role in modulating cellular metabolism. Intracellular metabolic profiling revealed that PknG is necessary for efficient metabolic adaptation during hypoxia. Notably, the PknG mutant exhibited a reductive shift in mycothiol redox potential and compromised stress response. Exposure to antibiotics and hypoxic environment resulted in higher oxidative shift in mycothiol redox potential of PknG mutant compared with the wild type. Persistence during latency-like conditions required kinase activity and thioredoxin motifs of PknG and is mediated through phosphorylation of a central metabolic regulator GarA. Finally, using a guinea pig model of infection, we assessed the in vivo role of PknG in manifestation of disease pathology and established a role for PknG in the formation of stable granuloma, hallmark structures of latent tuberculosis. Taken together, PknG-mediated GarA phosphorylation is important for maintenance of both mycobacterial physiology and redox poise, an axis that is dispensable for survival under normoxic conditions but is critical for non-replicating persistence of mycobacteria. In conclusion, we propose that PknG probably acts as a modulator of latency-associated signals.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:Hypoxia; Mycobacteria; Mycobacterium Tuberculosis; Redox Signaling; Serine/Threonine Protein Kinase; Thioredoxin
ID Code:113497
Deposited On:25 May 2018 07:15
Last Modified:25 May 2018 07:15

Repository Staff Only: item control page