Identification of two pyruvate transporters inSalmonella entericaserovar Typhimurium and their biological relevance

Abstract

SUMMARYPyruvate (CH3COCOOH) 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, inSalmonella entericaserovar Typhimurium (S. Typhimurium). Expression ofbtsTis induced by the histidine kinase/response regulator system BtsS/BtsR upon sensing extracellular pyruvate (threshold 200 μM), whereas expression ofcstAis 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 ofS. Typhimurium in response to gentamicin. Compared with the wild-type, the ΔbtsTΔcstAmutant 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 inS. Typhimurium.