Characterization of the Biological Effect Mediated by Mycobacterial Kinase PknG on Protein Phosphorylation and Acetylation

Tuberculosis (TB) remains a significant global public
health challenge,
with post-translational modifications (PTMs) in mycobacteria being
integral to physiological processes, pathogenesis, and drug resistance
mechanisms. Protein kinase G (PknG), the only reported secreted kinase
in mycobacteria, is associated with virulence, immune evasion, and
drug resistance. Nevertheless, the comprehensive range of proteins
and phosphorylation modifications regulated by PknG in mycobacteria
has not yet been fully elucidated. This study conducted a systematic
investigation into the dynamic alterations in the proteome and phosphoproteome
of mycobacteria following the overexpression of PknG. A comprehensive
analysis identified 3836 proteins and 467 phosphorylation sites, revealing
the regulatory role of MsPknG in energy metabolism
pathways and binding processes. Additionally, the study highlighted
the interplay between protein phosphorylation and lysine acetylation,
noting a reduction in lysine acetylation that is linked to carbon
metabolism and various energy-related pathways in the MsPknG overexpression strains. The role of MsPknG
in growth, infection, and the secretion of the inflammatory factor
was further investigated, providing new insights into phosphorylation
functions within mycobacteria and potential clinical targets for tuberculosis
treatment. The study additionally provides an innovative perspective
on the interplay between post-translational modifications in mycobacteria.