Figure 2.

S. aureus adaptation to specific immunometabolites impact host immunity. Left panel: Itaconate produced during infection inhibits S. aureus glycolysis. This rewires staphylococcal metabolism, promoting carbon flux through metabolic pathways that synthesize biofilms. S. aureus biofilms promote OXPHOS in macrophages and an anti-inflammatory phenotype. Middle panel: Lactate produced by S. aureus biofilm inhibits HDAC11 in macrophages and promotes anti-inflammatory IL-10 production. Right panel: Fumarate also inhibits glycolysis. In order to relieve the inhibition of glycolysis and ensure their survival, S. aureus SCVs increase their expression of fumC, which encodes the enzyme fumarate hydratase to degrade fumarate. SCV degradation of fumarate inhibits trained immunity through decreased methylation at the promoters of genes encoding proinflammatory cytokines such as IL-6. This impairs swift cytokine production upon re-stimulation.