Regulation of Salmonella pathogenicity island 2 genes by independent environmental signals

The function of a type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2 (SPI2) is essential for the intracellular lifestyle of Salmonella enterica serovar Typhimurium. Expression of SPI2 genes is induced within the Salmonella-containing vacuole (SCV) inside host cells and is controlled by the SsrAB two-component system. However, the nature of the signals leading to expression of SPI2 genes is controversial. Here we report that expression of SPI2 genes can be induced independently by two different environmental stimuli. Exposure of bacteria to slightly acidic pH was sufficient to induce a rapid up-regulation of SPI2 genes. In contrast, limitation of inorganic phosphate (Pi) in the growth media led to activation of SPI2 genes in the late exponential growth phase and was independent of the media pH. Limitation of Pi induced an over-expression of sensor protein SsrB. Response to both environmental stimuli required a functional SsrAB system. In vivo analyses indicated that limitation of Pi is also encountered by intracellular Salmonella. Our observations allow the integration of previous disparate reports on the induction of SPI2 genes.