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Updated: Sep 20, 2025

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Protein kinase G-a key regulator of pathogenesis in Mycobacterium tuberculosis infection
Anjali K Mahato1, Rupal Rai1, Rashmi Chourasia2
1Molecular Signalling Lab, Department of Biological Sciences and Engineering, Maulana Azad National Institute of Technology, Bhopal, MP, India.
Abstract:
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), remains a leading global health threat, exacerbated by rising drug resistance and the ability of this pathogen to persist within host macrophages. Central to the intracellular survival of M. tuberculosis is Protein Kinase G (PknG), a secreted, eukaryotic-like serine/threonine kinase that subverts host immune defenses and modulates bacterial physiology. This review provides a comprehensive overview of structural features and the multifaceted role of PknG in M. tuberculosis pathogenesis, including inhibition of phagosome-lysosome fusion, acid tolerance, metabolic reprogramming, autophagy suppression, and cell wall remodelling. Additionally, we discuss recent advancements in targeting PknG with small-molecule inhibitors, highlighting its promise as a therapeutic target. By delineating PknG's central role in host-pathogen interactions and stress adaptation, this review underscores its potential in shaping future anti-TB strategies, especially against drug-tolerant and latent infections..
Insights
Protein Kinase G (PknG) is crucial for Mycobacterium tuberculosis survival within host cells. Targeting PknG offers a promising strategy against drug-resistant tuberculosis and latent infections.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Tuberculosis (TB) remains a global health challenge, driven by drug-resistant Mycobacterium tuberculosis strains and pathogen persistence within macrophages.
- Protein Kinase G (PknG), a secreted serine/threonine kinase, is essential for M. tuberculosis intracellular survival and virulence.
Purpose of the Study:
- To provide a comprehensive review of PknG's structural features and its diverse roles in M. tuberculosis pathogenesis.
- To highlight recent advancements in developing PknG inhibitors as a potential therapeutic strategy against TB.
Main Methods:
- Literature review synthesizing existing research on PknG structure, function, and inhibition.
- Analysis of PknG's involvement in key pathogenic mechanisms like immune evasion and host cell modulation.
Main Results:
- PknG subverts host defenses by inhibiting phagosome-lysosome fusion, promoting acid tolerance, and suppressing autophagy.
- PknG plays a role in metabolic reprogramming and bacterial cell wall remodeling.
- Small-molecule inhibitors targeting PknG show therapeutic promise.
Conclusions:
- PknG is a central mediator of M. tuberculosis pathogenesis and host-pathogen interactions.
- Targeting PknG represents a viable strategy for developing novel anti-TB therapies, particularly for drug-tolerant and latent infections.
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