Host succinate is an activation signal for Salmonella virulence during intracellular infection

Salmonella profits from immunometabolism Extensive metabolic rewiring occurs in various immune cells during the course of infection. Whether these changes can be exploited by intracellular pathogens remains an open question. Rosenberg et al. report that infection with Salmonella enterica serovar Typhimurium ( S. Tm) induces the accumulation of the metabolite succinate in macrophages (see the Perspective by Lynch and Lesser). This key intermediate in the citric acid cycle activates virulence genes in S. Tm, leading to microbial resistance. Moreover, the active transport of succinate through the C4-dicarboxylate transporter DcuB is required for S. Tm virulence and survival within macrophages. Sensing of citric acid cycle intermediates may more generally serve as a cue to initiate the resistance programs of intracellular pathogens. Science , this issue p. 400 ; see also p. 344