Quantitative Proteomics Combined with Phosphoproteome Reveals the Mechanism of the Density-Sensing Regulator QseC in the Pathogenesis of Glaesserella parasuis

QseC
is a sensor component of the two-component system
(TCS) QseBC
in Glaesserella parasuis (G. parasuis). Quantitative proteomics identifies
39 differentially expressed proteins (DEPs) (12 upregulated, 27 downregulated)
in ΔqseC, with the lipid metabolism enzyme
PlsB emerging as a core hub showing concurrent upregulation in total
protein expression and phosphorylation. Phosphoproteomics detects
95 phosphorylation sites, demonstrating predominant serine phosphorylation
(40%) and significant PlsB/SerS hyperphosphorylation. Functional analyses
show that deleting the qseC gene disrupts cellular balance. This change
causes an energy crisis involving ATPase imbalance and carbohydrate
metabolism defects. It also weakens the cell membrane by reducing
key lipopolysaccharide (LPS) biosynthesis proteins like LpxB, KdsB,
and WaaQ. Additionally, iron uptake becomes impaired because genes
such as hemG and fbpC2 are suppressed, along with defense proteins
HsdR and ApxIB. Finally, cells adopt an “offensive-defensive
shift” survival strategy. They do this by reducing energy-intensive
defenses like UvrA-mediated DNA repair and β-lactam resistance,
while increasing lipid storage (PlsB) and RNA degradation. Protein–protein
interaction (PPI) networks confirm 10 core proteins that collectively
maintain proteostasis and stress adaptation, with PlsB serving as
the central coordinator of membrane synthesis and environmental adaptation.