CidC and AlsSD carbon overflow pathways modulate cell death.

(A) Schematic of overflow metabolic pathways controlled by the LysR-type transcriptional regulator, CidR. Under aerobic conditions and in the presence of glucose, acetyl CoA derived from the decarboxylation of pyruvate by Pdh (pyruvate dehydrogenase) is converted to acetate by the Pta (phosphotransacetylase)/AckA (acetate kinase) pathway (black). Excess glucose can activate additional metabolic pathways (CidR regulated; blue) that divert pyruvate towards the production of acetate (red) and the neutral metabolite, acetoin (green) through CidC (pyruvate oxidase) and AlsSD (α-acetolactate synthase/α-acetolactate decarboxylase) enzyme activities, respectively. The concentrations of acetate (B) and acetoin (C) were determined from culture supernatants of various S. aureus strains after 24 h of growth in TSB-35 mM glucose using commercially available kits (R-Biopharm, Germany). Statistical significance was assessed using one way ANOVA followed by Newman Kewl's multiple post-comparison test, n = 3; * P<0.05, ** P<0.005). Stationary phase cell viability (D), flow cytometry of HPF/CTC double stained samples (E), EPR analysis (F) and TUNEL staining (G) were determined following aerobic growth of cultures in TSB-35 mM glucose.