The Biological Significance of Pyruvate Sensing and Uptake in Salmonella enterica Serovar Typhimurium

Pyruvate (CH(3)COCOOH) is the simplest of the alpha-keto acids and is at the interface of several metabolic pathways both in prokaryotes and eukaryotes. In an amino acid-rich environment, fast-growing bacteria excrete pyruvate instead of completely metabolizing it. The role of pyruvate uptake in pathological conditions is still unclear. In this study, we identified two pyruvate-specific transporters, BtsT and CstA, in Salmonella enterica serovar Typhimurium (S. Typhimurium). Expression of btsT is induced by the histidine kinase/response regulator system BtsS/BtsR upon sensing extracellular pyruvate, whereas expression of cstA is maximal in the stationary phase. Both pyruvate transporters were found to be important for the uptake of this compound, but also for chemotaxis to pyruvate, survival under oxidative and nitrosative stress, and persistence of S. Typhimurium in response to gentamicin. Compared with the wild-type cells, the ΔbtsTΔcstA mutant has disadvantages in antibiotic persistence in macrophages, as well as in colonization and systemic infection in gnotobiotic mice. These data demonstrate the surprising complexity of the two pyruvate uptake systems in S. Typhimurium.