Adaptation of Salmonella typhimurium to the macrophages metabolic switch during host pathogen interaction

Macrophages function as the first line of immune defense against invading pathogens. During host pathogen interaction, exposure of macrophages to pathogen-associated molecular patterns (PAMPs), leads to a rapid switch in cell metabolism from oxidative phosphorylation that is done in the mitochondria, to high rate glycolysis in the cell cytosol. This metabolic reprograming leads to elevation of proinflammatory cytokines secretion and generation of mitochondrial reactive oxygen species that together contribute to efficient bacterial elimination. The intracellular gram negative pathogen Salmonella typhimurium has evolved to survive a wide range of environments and multiple hosts, but the mechanism that enables adaptation of Salmonella to the macrophages metabolic shift remains elusive. Using novel and cutting edge RNA sequencing method that allows simultaneous analysis of host and pathogen transcripts, we analyzed the macrophage - Salmonella interaction under changing metabolic environments. We reveal host metabolic signals that are used by Salmonella to optimize its virulence and intracellular survival.