Protein kinase G-a key regulator of pathogenesis in Mycobacterium tuberculosis infection.

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..