OmpR regulates the two-component system SsrA-SsrB in Salmonella pathogenicity island 2

Salmonella pathogenicity island 2 (SPI-2) encodes a putative, two-component regulatory system, SsrA-SsrB, which regulates a type III secretion system needed for replication inside macrophages and systemic infection in mice. T he sensor and regulator homologs, ssrAB (spiR), and genes within the secret ion system, including the structural gene ssaH, are transcribed after Salmo nella enters host cells. We have studied the transcriptional regulation of ssrAB and the secretion system by using gfp fusions to the ssrA and ssaH pr omoters. We found that early transcription of ssrA, after entry into macrop hages, is most efficient in the presence of OmpR. An ompR mutant strain doe s not exhibit replication within cultured macrophages. Furthermore, footpri nt analysis shows that purified OmpR protein binds directly to the ssrA pro moter region. We also show that minimal medium, pH 4.5, induces SPI-2 gene expression in wild-type but not ompR mutant strains. We conclude that the t ype III secretion system of SPI-2 is regulated by OmpR, which activates exp ression of ssrA soon after Salmonella enters the macrophage.