Quantitative Proteomics Charts the Landscape of Salmonella Carbon Metabolism within Host Epithelial Cells

We performed a proteomic survey of Salmonella enterica serovar Typhimurium during infection of host epithelial cells. Our data reveal substantial metabolic reshuffling of Salmonella in the host in addition to severe degeneration of bacterial flagella and chemotaxis systems. The large-scale quantitative data allowed us to chart an overview of intracellular Salmonella carbon metabolism. Notably, we found preferential utilization of glycolysis, the pentose phosphate pathway, mixed acid fermentation, and nucleotide metabolism. In contrast, the tricarboxylic acid (TCA) cycle and aerobic and anaerobic respiration pathways were largely repressed. Furthermore, inactivation of glycolysis and purine biosynthesis led to severe growth defects, indicating important roles in intracellular Salmonella replication. In summary, we exploited quantitative proteomics for rational design of follow-up genetic studies and identified pathways important for bacterial fitness within host cells.