PRJNA561041
Host Metabolic Reprogramming Regulates and Fuels Salmonella Typhimurium Replication in Macrophage
Salmonella Typhimurium (STM) relies on its replication in macrophages to establish systemic infection. Upon sensing of microbial ligands, macrophage undergoes metabolic reprograming whereby increased glycolysis drives antimicrobial inflammation to combat invading pathogens. Through transcriptome, metabolome, and many other molecular techniques, we demonstrate STM promotes macrophage glycolysis while represses serine synthesis to accumulate glycolytic intermediates for its intracellular replication and systemic infection. Intracellular STM uses three of the accumulated glycolytic intermediates as carbon source, via sensing of the decreased host glucose to initiate the import of these intermediates. Moreover, STM exploits two others intermediates as signals to induce the expression of Salmonella pathogenicity island (SPI-2) type III secretion system, which is required for STM intracellular replication. Our findings provide a paradigm for intracellular pathogens through modulating and exploiting the macrophage metabolic reprogramming for intracellular replication and pathogenicity.