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

QseC is a sensor component of the two-component system (TCS) QseBC in (). Quantitative proteomics identifies 39 differentially expressed proteins (DEPs) (12 upregulated, 27 downregulated) in Δ, 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.