A Proteomic View of Salmonella Typhimurium in Response to Phosphate Limitation

Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, often encounters phosphate (P(i)) shortage both in the environment and inside host cells. To gain a global view on its physiological responses to P(i) starvation, we performed proteomic profiling of S. Typhimurium upon the shift from P(i)-rich to P(i)-low conditions. In addition to the Pho regulon, many metabolic processes were up-regulated, such as glycolysis, pentose phosphate pathway, pyrimidine degradation, glycogen, and trehalose metabolism, allowing us to chart an overview of S. Typhimurium carbon metabolism under P(i) starvation. Furthermore, proteomic analysis of a mutant lacking phoB (that encodes a key regulator of P(i) shortage response) suggested that only a small subset of the altered proteins upon P(i) limitation was PhoB-dependent. Importantly, we present evidence that S. Typhimurium N-acetylglucosamine catabolism was induced under P(i)-limiting conditions in a PhoB-dependent manner. Immunoblotting and β-galactosidase assays demonstrated that PhoB was required for the full activation of NagB, a key enzyme of this pathway, in response to low P(i). Thus, our study reveals that N-acetylglucosamine catabolism may represent an additional PhoB-regulated pathway to tackle bacterial P(i) shortage.