Quantitative Proteomic Analysis of Salmonella enterica Serovar Typhimurium under PhoP/PhoQ Activation Conditions

The PhoP/PhoQ two-component system plays a central regulatory role in the pathogenesis of Salmonella enterica serovar Typhimurium (S. Typhimurium), and it can be activated by low Mg2+ concentrations and sublethal concentrations of cationic antimicrobial peptides (CAMP). Therefore, these two PhoP/PhoQ activation signals are considered as in vivo environmental cues sensed by S. Typhimurium for adaptation and survival. In this work, we conducted a SILAC (stable isotope labeling by amino acids in cell culture)-based quantitative proteomic study to survey the proteomic changes of S. Typhimurium in response to low Mg2+ concentrations or CAMP. We discovered that CAMP activated a portion of the PhoP/PhoQ regulatory network, whereas low Mg2+ concentrations upregulated nearly all known members of this network, a number of previously unknown proteins, and some proteins regulated by IHF and RpoS. Systematic analysis following metabolic pathways revealed that low Mg2+ concentrations selectively influenced proteins of certain metabolic functions while CAMP did not. Our study indicates that the low Mg2+-concentration condition may lead S. Typhimurium into a growth-control lifestyle, which provides new perspectives about Salmonella’s adaptation to the host environment.