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.